Co-delivery　of　anti-inflammatory　drugs　and　reactive　oxygen　species　(ROS)　scavengers　by　stimuli-responsive　oral　nanoparticles　is　deemed　to　be　a　favorable　strategy　for　inflammatory　bowel　disease　(IBD)　therapy.　In　this　study,　using　micelles　formed　by　CUR　conjugated　hydroxyethyl　starch　(HES)　as　vehicles,　dexamethasone　(DEX)-loaded　HES-CUR　nanoparticles　(DHC　NPs)　with　desirable　size,　negative　surface　charge,　good　stability　in　the　harsh　gastric　environment,　and　excellent　ROS　scavenging　activity　are　developed　as　a　colon-targeted　oral　formulation　for　treating　IBD.　Due　to　the　degradation　of　HES　in　response　to　α-amylase　overexpressed　in　the　inflamed　colon,　the　DHC　NPs　release　drugs　in　an　α-amylase-responsive　manner.　Meanwhile,　the　DHC　NPs　can　be　effectively　internalized　by　macrophages　and　show　excellent　cytocompatibility　with　macrophages　since　they　are　composed　of　food-derived　compounds.　Importantly,　in　vivo　studies　reveal　that　the　DHC　NPs　are　capable　of　targeting　the　inflamed　colon　induced　by　dextran　sulfate　sodium　(DSS),　and　the　targeted　and　combination　therapy　enhances　the　efficacy　of　free　DEX　and　significantly　relieves　the　impairment　caused　by　DSS-induced　ulcerative　colitis.　Incorporating　the　merits　of　targeted　drug　delivery　and　combined　therapy　with　an　anti-inflammatory　drug　and　ROS　scavenger,　the　DHC　NPs　are　promising　for　developing　novel　oral　formulations　for　IBD　therapy.　©　2022　Elsevier　B.V.