<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2019 Workiva-->
<!--r:dd3d45a7-0da8-47bb-a3c3-61f8520e369a,g:f14ad036-b762-448e-8dce-df34663fa9a4-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:dnli="http://www.denalitherapeutics.com/20190930" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:nonnum="http://www.xbrl.org/dtr/type/non-numeric" xmlns:num="http://www.xbrl.org/dtr/type/numeric" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:link="http://www.xbrl.org/2003/linkbase" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.denalitherapeutics.com/20190930">
  <xs:import namespace="http://fasb.org/srt/2019-01-31" schemaLocation="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2019-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd"/>
  <xs:import namespace="http://www.w3.org/1999/xlink" schemaLocation="http://www.xbrl.org/2003/xlink-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/non-numeric" schemaLocation="http://www.xbrl.org/dtr/type/nonNumeric-2009-12-16.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/numeric" schemaLocation="http://www.xbrl.org/dtr/type/numeric-2009-12-16.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2019-01-31" schemaLocation="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd"/>
  <xs:element id="dnli_RetainedActivitiesMember" abstract="true" name="RetainedActivitiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_HeadquartersLeaseMember" abstract="true" name="HeadquartersLeaseMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_LicenseAgreementMilestonePaymentUponAchievementOfClinicalAndRegulatoryMilestones" abstract="false" name="LicenseAgreementMilestonePaymentUponAchievementOfClinicalAndRegulatoryMilestones" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_OperatingLeasesAreaUnderLease" abstract="false" name="OperatingLeasesAreaUnderLease" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="num:areaItemType"/>
  <xs:element id="dnli_IncreaseDecreaseInNonCashOperatingLeaseExpense" abstract="false" name="IncreaseDecreaseInNonCashOperatingLeaseExpense" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_OrganizationAndDescriptionOfBusinessPolicyPolicyTextBlock" abstract="false" name="OrganizationAndDescriptionOfBusinessPolicyPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:textBlockItemType"/>
  <xs:element id="dnli_CNSProductMember" abstract="true" name="CNSProductMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_TwoThousandSeventeenEquityIncentivePlanMember" abstract="true" name="TwoThousandSeventeenEquityIncentivePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_PeripheralProductMember" abstract="true" name="PeripheralProductMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_PurchaseOrderExecuted" abstract="false" name="PurchaseOrderExecuted" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_PreclinicalMilestonePaymentReceived" abstract="false" name="PreclinicalMilestonePaymentReceived" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_AssetAcquisitionTextBlock" abstract="false" name="AssetAcquisitionTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:textBlockItemType"/>
  <xs:element id="dnli_AggregateDevelopmentMilestonePayment" abstract="false" name="AggregateDevelopmentMilestonePayment" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ForeignExchangeForwardSwissFrancsMember" abstract="true" name="ForeignExchangeForwardSwissFrancsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_SharebasedCompensationArrangementBySharebasedPaymentAwardNumberOfAdditionalSharesAllowableUnderThePlan" abstract="false" name="SharebasedCompensationArrangementBySharebasedPaymentAwardNumberOfAdditionalSharesAllowableUnderThePlan" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="dnli_PerformanceAndMarketShareBasedCompensation" abstract="false" name="PerformanceAndMarketShareBasedCompensation" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_NumberOfIndications" abstract="false" name="NumberOfIndications" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="dnli_CollaborativeArrangementWithFStarAndAcquisitionOfFStarGammaMember" abstract="true" name="CollaborativeArrangementWithFStarAndAcquisitionOfFStarGammaMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_SharePurchaseAgreementMember" abstract="true" name="SharePurchaseAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_StockIssuedDuringPeriodValueCollaborationAgreement" abstract="false" name="StockIssuedDuringPeriodValueCollaborationAgreement" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_AggregateOptionExerciseFee" abstract="false" name="AggregateOptionExerciseFee" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_LicenseAgreementMember" abstract="true" name="LicenseAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_EmployeeAndNonEmployeeStockOptionMember" abstract="true" name="EmployeeAndNonEmployeeStockOptionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_LongTermMarketableSecuritiesMember" abstract="true" name="LongTermMarketableSecuritiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_UpfrontPayments" abstract="false" name="UpfrontPayments" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_SignificantAccountingPoliciesLineItems" abstract="true" name="SignificantAccountingPoliciesLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="dnli_PaymentsForManufacturingCost" abstract="false" name="PaymentsForManufacturingCost" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedAndExpectedToVestOutstandingNumber" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedAndExpectedToVestOutstandingNumber" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="dnli_ProceedsFromIssuanceOfCommonStockInConnectionWithCollaborationAgreement" abstract="false" name="ProceedsFromIssuanceOfCommonStockInConnectionWithCollaborationAgreement" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_StockIssuedDuringPeriodSharesEquityIncentivePlan" abstract="false" name="StockIssuedDuringPeriodSharesEquityIncentivePlan" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="dnli_LandlordFundedTenantImprovementsMember" abstract="true" name="LandlordFundedTenantImprovementsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_SanofiCollaborationAgreementMember" abstract="true" name="SanofiCollaborationAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_ForeignExchangeForwardBritishPoundsMember" abstract="true" name="ForeignExchangeForwardBritishPoundsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_ContingentPaymentsUponAchievementOfMilestones" abstract="false" name="ContingentPaymentsUponAchievementOfMilestones" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_PerformanceAndMarketShareBasedCompensationCompensationCostNotYetRecognized" abstract="false" name="PerformanceAndMarketShareBasedCompensationCompensationCostNotYetRecognized" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_SanofiMember" abstract="true" name="SanofiMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_CollaborativeArrangementPayment" abstract="false" name="CollaborativeArrangementPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_TargetOptionPeriod" abstract="false" name="TargetOptionPeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="dnli_SignificantAccountingPoliciesTable" abstract="true" name="SignificantAccountingPoliciesTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="dnli_UpfrontOptionFee" abstract="false" name="UpfrontOptionFee" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_SaleOfStockConsiderationPremiumReceivedOnTransaction" abstract="false" name="SaleOfStockConsiderationPremiumReceivedOnTransaction" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_DenaliMember" abstract="true" name="DenaliMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_TakedaPharmaceuticalCompanyLimitedMember" abstract="true" name="TakedaPharmaceuticalCompanyLimitedMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_TwoThousandFifteenEquityIncentivePlanMember" abstract="true" name="TwoThousandFifteenEquityIncentivePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_MaximumDevelopmentPlanPeriodForResearchCosts" abstract="false" name="MaximumDevelopmentPlanPeriodForResearchCosts" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="dnli_RestrictedSharesSubjectToFutureVestingMember" abstract="true" name="RestrictedSharesSubjectToFutureVestingMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_LongTermInvestmentsMember" abstract="true" name="LongTermInvestmentsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_ContingentConsiderationPayment" abstract="false" name="ContingentConsiderationPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ForeignExchangeForwardEurosMember" abstract="true" name="ForeignExchangeForwardEurosMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_CommercialMilestonePayments" abstract="false" name="CommercialMilestonePayments" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_NumberOfTargets" abstract="false" name="NumberOfTargets" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="dnli_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingDaysAfterInitialPublicOffering" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingDaysAfterInitialPublicOffering" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="dnli_PerformanceAndMarketContingentStockOptionsMember" abstract="true" name="PerformanceAndMarketContingentStockOptionsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_IncreaseDecreaseInDeferredRent" abstract="false" name="IncreaseDecreaseInDeferredRent" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_StockIssuedDuringPeriodValueEquityIncentivePlan" abstract="false" name="StockIssuedDuringPeriodValueEquityIncentivePlan" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_NewPremisesSubleaseAgreementMember" abstract="true" name="NewPremisesSubleaseAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_OperatingLeasesSubleaseNetRentableArea" abstract="false" name="OperatingLeasesSubleaseNetRentableArea" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="num:areaItemType"/>
  <xs:element id="dnli_AggregateClinicalRegulatoryAndSalesMilestonePayment" abstract="false" name="AggregateClinicalRegulatoryAndSalesMilestonePayment" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_CollaborationAgreementTransactionPriceIncrease" abstract="false" name="CollaborationAgreementTransactionPriceIncrease" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_PreclinicalMilestonePaymentPerProgram" abstract="false" name="PreclinicalMilestonePaymentPerProgram" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_AlzheimersDiseaseServicesMember" abstract="true" name="AlzheimersDiseaseServicesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_LicenseAgreementTextBlock" abstract="false" name="LicenseAgreementTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:textBlockItemType"/>
  <xs:element id="dnli_CommercialMilestonesPerProgram" abstract="false" name="CommercialMilestonesPerProgram" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_InitialOptionExercisePayments" abstract="false" name="InitialOptionExercisePayments" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_PreclinicalMilestonePaymentEarnedNotYetReceived" abstract="false" name="PreclinicalMilestonePaymentEarnedNotYetReceived" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_StockIssuedDuringPeriodSharesCollaborationAgreement" abstract="false" name="StockIssuedDuringPeriodSharesCollaborationAgreement" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="dnli_TwoThousandAndSeventeenEmployeeStockPurchasePlanMember" abstract="true" name="TwoThousandAndSeventeenEmployeeStockPurchasePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_UpfrontFeesPaid" abstract="false" name="UpfrontFeesPaid" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ConstrainedVariableConsideration" abstract="false" name="ConstrainedVariableConsideration" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_RegulatoryMilestonePayment" abstract="false" name="RegulatoryMilestonePayment" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_NumberOfPrograms" abstract="false" name="NumberOfPrograms" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="dnli_GenentechIncMember" abstract="true" name="GenentechIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_AggregatePreclinicalMilestonePayment" abstract="false" name="AggregatePreclinicalMilestonePayment" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_EarlyExercisedCommonStockSubjectToFutureVestingMember" abstract="true" name="EarlyExercisedCommonStockSubjectToFutureVestingMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_ClinicalMilestonePayment" abstract="false" name="ClinicalMilestonePayment" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ShortTermMarketableSecuritiesMember" abstract="true" name="ShortTermMarketableSecuritiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_TenantImprovementAllowanceRepayableAsRent" abstract="false" name="TenantImprovementAllowanceRepayableAsRent" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_LesseeOperatingLeaseRenewalNoticePeriod" abstract="false" name="LesseeOperatingLeaseRenewalNoticePeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="dnli_AggregateCommercialMilestones" abstract="false" name="AggregateCommercialMilestones" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_PerformanceAndMarketShareBasedCompensationCompensationCostNotYetRecognizedPeriodOfRecognition" abstract="false" name="PerformanceAndMarketShareBasedCompensationCompensationCostNotYetRecognizedPeriodOfRecognition" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="dnli_RevenueNumberOfPerformanceObligations" abstract="false" name="RevenueNumberOfPerformanceObligations" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="dnli_CollaborativeAgreementFundedPercentage" abstract="false" name="CollaborativeAgreementFundedPercentage" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="num:percentItemType"/>
  <xs:element id="dnli_SharesTransferredAsAvailableForIssuanceFromTwoThousandFifteenPlanToTwoThousandSeventeenPlanMember" abstract="true" name="SharesTransferredAsAvailableForIssuanceFromTwoThousandFifteenPlanToTwoThousandSeventeenPlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueExpectedToVest" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueExpectedToVest" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="num:perShareItemType"/>
  <xs:element id="dnli_MilestoneTriggeredMember" abstract="true" name="MilestoneTriggeredMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_LesseeFinanceLeaseNumberOfContracts" abstract="false" name="LesseeFinanceLeaseNumberOfContracts" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="dnli_ProceedsForClinicalMilestone" abstract="false" name="ProceedsForClinicalMilestone" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_DMSAMember" abstract="true" name="DMSAMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_VariableConsiderationFutureConsideration" abstract="false" name="VariableConsiderationFutureConsideration" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_AssetAcquisitionContingentConsiderationAmountRecognized" abstract="false" name="AssetAcquisitionContingentConsiderationAmountRecognized" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ExerciseOfBuyoutOptionMember" abstract="true" name="ExerciseOfBuyoutOptionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_TakedaCollaborationAgreementMember" abstract="true" name="TakedaCollaborationAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="nonnum:domainItemType"/>
  <xs:element id="dnli_OptionFeesPerProgram" abstract="false" name="OptionFeesPerProgram" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="dnli_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardThresholdConsecutiveTradingDays" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardThresholdConsecutiveTradingDays" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="dnli_NoncashTenantImprovementsPaidByLandlord" abstract="false" name="NoncashTenantImprovementsPaidByLandlord" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="dnli-20190930_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="dnli-20190930_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="dnli-20190930_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="dnli-20190930_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="DocumentandEntityInformation" roleURI="http://www.denalitherapeutics.com/role/DocumentandEntityInformation">
        <link:definition>0001001 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedBalanceSheets" roleURI="http://www.denalitherapeutics.com/role/CondensedConsolidatedBalanceSheets">
        <link:definition>1001002 - Statement - Condensed Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedBalanceSheetsParenthetical" roleURI="http://www.denalitherapeutics.com/role/CondensedConsolidatedBalanceSheetsParenthetical">
        <link:definition>1002003 - Statement - Condensed Consolidated Balance Sheets (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofOperationsandComprehensiveLoss" roleURI="http://www.denalitherapeutics.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveLoss">
        <link:definition>1003004 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofStockholdersEquity" roleURI="http://www.denalitherapeutics.com/role/ConsolidatedStatementsofStockholdersEquity">
        <link:definition>1004005 - Statement - Consolidated Statements of Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofCashFlows" roleURI="http://www.denalitherapeutics.com/role/ConsolidatedStatementsofCashFlows">
        <link:definition>1005006 - Statement - Consolidated Statements of Cash Flows</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAccountingPolicies" roleURI="http://www.denalitherapeutics.com/role/SignificantAccountingPolicies">
        <link:definition>2101101 - Disclosure - Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAccountingPoliciesPolicies" roleURI="http://www.denalitherapeutics.com/role/SignificantAccountingPoliciesPolicies">
        <link:definition>2202201 - Disclosure - Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAccountingPoliciesNarrativeDetails" roleURI="http://www.denalitherapeutics.com/role/SignificantAccountingPoliciesNarrativeDetails">
        <link:definition>2403401 - Disclosure - Significant Accounting Policies - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurements" roleURI="http://www.denalitherapeutics.com/role/FairValueMeasurements">
        <link:definition>2104102 - Disclosure - Fair Value Measurements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsTables" roleURI="http://www.denalitherapeutics.com/role/FairValueMeasurementsTables">
        <link:definition>2305301 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsDetails" roleURI="http://www.denalitherapeutics.com/role/FairValueMeasurementsDetails">
        <link:definition>2406402 - Disclosure - Fair Value Measurements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashandMarketableSecurities" roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecurities">
        <link:definition>2107103 - Disclosure - Cash and Marketable Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashandMarketableSecuritiesTables" roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesTables">
        <link:definition>2308302 - Disclosure - Cash and Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashandMarketableSecuritiesScheduleofRestrictedCashandCashEquivalentsDetails" roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesScheduleofRestrictedCashandCashEquivalentsDetails">
        <link:definition>2409403 - Disclosure - Cash and Marketable Securities - Schedule of Restricted Cash and Cash Equivalents (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashandMarketableSecuritiesSummaryofAvailableforSaleSecuritiesDetails" roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesSummaryofAvailableforSaleSecuritiesDetails">
        <link:definition>2410404 - Disclosure - Cash and Marketable Securities - Summary of Available for Sale Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashandMarketableSecuritiesNarrativeDetails" roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesNarrativeDetails">
        <link:definition>2411405 - Disclosure - Cash and Marketable Securities - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="DerivativeFinancialInstruments" roleURI="http://www.denalitherapeutics.com/role/DerivativeFinancialInstruments">
        <link:definition>2112104 - Disclosure - Derivative Financial Instruments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="DerivativeFinancialInstrumentsTables" roleURI="http://www.denalitherapeutics.com/role/DerivativeFinancialInstrumentsTables">
        <link:definition>2313303 - Disclosure - Derivative Financial Instruments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="DerivativeFinancialInstrumentsSummaryofForwardForeignCurrencyExchangeContractsOutstandingDetails" roleURI="http://www.denalitherapeutics.com/role/DerivativeFinancialInstrumentsSummaryofForwardForeignCurrencyExchangeContractsOutstandingDetails">
        <link:definition>2414406 - Disclosure - Derivative Financial Instruments - Summary of Forward Foreign Currency Exchange Contracts Outstanding (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Acquisition" roleURI="http://www.denalitherapeutics.com/role/Acquisition">
        <link:definition>2115105 - Disclosure - Acquisition</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AcquisitionDetails" roleURI="http://www.denalitherapeutics.com/role/AcquisitionDetails">
        <link:definition>2416407 - Disclosure - Acquisition (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreements" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreements">
        <link:definition>2117106 - Disclosure - Collaboration Agreements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreementsTables" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsTables">
        <link:definition>2318304 - Disclosure - Collaboration Agreements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreementsSanofiDetails" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiDetails">
        <link:definition>2419408 - Disclosure - Collaboration Agreements - Sanofi (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreementsSanofiPerformanceObligationDetails" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiPerformanceObligationDetails">
        <link:definition>2420409 - Disclosure - Collaboration Agreements - Sanofi Performance Obligation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreementsTakedaDetails" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsTakedaDetails">
        <link:definition>2421410 - Disclosure - Collaboration Agreements - Takeda (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreementsSummaryofCollaborationRevenueDetails" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSummaryofCollaborationRevenueDetails">
        <link:definition>2422411 - Disclosure - Collaboration Agreements - Summary of Collaboration Revenue (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LicenseAgreements" roleURI="http://www.denalitherapeutics.com/role/LicenseAgreements">
        <link:definition>2123107 - Disclosure - License Agreements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LicenseAgreementsDetails" roleURI="http://www.denalitherapeutics.com/role/LicenseAgreementsDetails">
        <link:definition>2424412 - Disclosure - License Agreements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingencies" roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingencies">
        <link:definition>2125108 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesTables" roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesTables">
        <link:definition>2326305 - Disclosure - Commitments and Contingencies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesNarrativeDetails" roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesNarrativeDetails">
        <link:definition>2427413 - Disclosure - Commitments and Contingencies - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails" roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails">
        <link:definition>2428414 - Disclosure - Commitments and Contingencies - Summary of Company's Future Minimum Lease Commitments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails_1" roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails_1">
        <link:definition>2428414 - Disclosure - Commitments and Contingencies - Summary of Company's Future Minimum Lease Commitments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseReceivablesDetails" roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseReceivablesDetails">
        <link:definition>2429415 - Disclosure - Commitments and Contingencies - Summary of Company's Future Minimum Lease Receivables (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwards" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwards">
        <link:definition>2130109 - Disclosure - Stock-Based Awards</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwardsTables" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsTables">
        <link:definition>2331306 - Disclosure - Stock-Based Awards (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwardsNarrativeDetails" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsNarrativeDetails">
        <link:definition>2432416 - Disclosure - Stock-Based Awards - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwardsSummaryofStockOptionActivityDetails" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofStockOptionActivityDetails">
        <link:definition>2433417 - Disclosure - Stock-Based Awards - Summary of Stock Option Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwardsSummaryofAssumptionsUsedforEstimatingtheFairValueofStockOptionsGrantedDetails" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofAssumptionsUsedforEstimatingtheFairValueofStockOptionsGrantedDetails">
        <link:definition>2434418 - Disclosure - Stock-Based Awards - Summary of Assumptions Used for Estimating the Fair Value of Stock Options Granted (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwardsSummaryofRestrictedStockActivityDetails" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofRestrictedStockActivityDetails">
        <link:definition>2435419 - Disclosure - Stock-Based Awards - Summary of Restricted Stock Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedAwardsSummaryofStockBasedCompensationExpenseDetails" roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofStockBasedCompensationExpenseDetails">
        <link:definition>2436420 - Disclosure - Stock-Based Awards - Summary of Stock-Based Compensation Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShare" roleURI="http://www.denalitherapeutics.com/role/NetLossPerShare">
        <link:definition>2137110 - Disclosure - Net Loss Per Share</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShareTables" roleURI="http://www.denalitherapeutics.com/role/NetLossPerShareTables">
        <link:definition>2338307 - Disclosure - Net Loss Per Share (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShareScheduleofDilutiveSecuritiesNotIncludedinDilutedPerShareCalculationsDetails" roleURI="http://www.denalitherapeutics.com/role/NetLossPerShareScheduleofDilutiveSecuritiesNotIncludedinDilutedPerShareCalculationsDetails">
        <link:definition>2439421 - Disclosure - Net Loss Per Share - Schedule of Dilutive Securities Not Included in Diluted Per Share Calculations (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationAgreementsSanofiPerformanceObligationDetailsDefault" roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiPerformanceObligationDetailsDefault">
        <link:definition>2420409 - Disclosure - Collaboration Agreements - Sanofi Performance Obligation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
</xs:schema>
