BACKGROUND: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy. METHODS: CeO@PDA-PEG (CeO@PP) were synthesized by modifying ceria (CeO) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model. RESULTS: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO nanorods with excellent dispersibility and colloidal stability. CeO@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury. CONCLUSION: The nanoplatform CeO@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.