Ulcerative colitis (UC) is a refractory chronic inflammatory disease involving the colon and rectum, falling under the category of inflammatory bowel disease (IBD). The accumulation of reactive oxygen species (ROS) in local tissues has been identified as a crucial contributor to the escalation of inflammatory responses. Therefore, eliminating ROS in the inflamed colon is a promising approach to treating UC. Nanomaterials with intrinsic enzyme-like activities (nanozymes) have shown significant therapeutic potential in UC. In this study, we found that platinum nanoparticles (Pt NPs) exhibited remarkable superoxide dismutase (SOD) and catalase (CAT) cascade catalytic activities, as well as effective hydroxyl radical (•OH) scavenging ability. The in vitro experiments showed that Pt NPs could eliminate excessive ROS to protect cells against oxidative stress. In the colitis model, oral administration of Pt NPs (loaded in chitosan/alginate hydrogel) could significantly alleviate UC, including reducing the colon length, the damaged epithelium, and the infiltration of inflammatory cells. Without appreciable systemic toxicity, Pt NPs represent a novel therapeutic approach to UC and are expected to achieve long-term inflammatory remission.