Polymeric　prodrugs,　synthesized　by　conjugating　chemotherapeutic　agents　to　functional　polymers,　have　been　extensively　investigated　and　employed　for　safer　and　more　efficacious　cancer　therapy.　By　rational　design,　a　pH　and　reduction　dual-sensitive　dextran-di-drugs　conjugate　(oDex-g-Pt+DOX)　was　synthesized　by　the　covalent　conjugation　of　Pt　(IV)　prodrug　and　doxorubicin　(DOX)　to　an　oxidized　dextran　(oDex).　Pt　(IV)　prodrug　and　DOX　were　linked　by　the　versatile　efficient　esterification　reactions　and　Schiff　base　reaction,　respectively.　oDex-g-Pt+DOX　could　self-assemble　into　nanoparticles　with　an　average　diameter　at　around　180　nm.　The　acidic　and　reductive　(GSH)　environment　induced　degradation　and　drug　release　behavior　of　the　resulting　nanoparticles　(oDex-g-Pt+DOX　NPs)　were　systematically　investigated　by　optical　experiment,　DLS　analysis,　TEM　measurement,　and　in　vitro　drugs　release　experiment.　Effective　cellular　uptake　of　the　oDex-g-Pt+DOX　NPs　was　identified　by　the　human　cervical　carcinoma　HeLa　cells　via　confocal　laser　scanning　microscopy.　Furthermore,　oDex-g-Pt+DOX　NPs　displayed　a　comparable　antiproliferative　activity　than　the　simple　combination　of　free　cisplatin　and　DOX　(Cis+DOX)　as　the　extension　of　time.　More　importantly,　oDex-g-Pt+DOX　NPs　exhibited　remarkable　reversal　ability　of　tumor　resistance　compared　to　the　cisplatin　in　cisplatin-resistant　lung　carcinoma　A549　cells.　Take　advantage　of　the　acidic　and　reductive　microenvironment　of　tumors,　this　smart　polymer-dual-drugs　conjugate　could　serve　as　a　promising　and　effective　nanomedicine　for　combination　chemotherapy.