In this study, FeMoO(4)/MoO(3) nanoparticles (Fe/Mo NPs) were coated with mannose-modified chitosan (CM) to form Fe/Mo@CM nanozyme. Fe/Mo@CM exhibited strong self-cascading multiple antioxidant enzyme-mimicking activities. It simulated the natural antioxidant defense system composed of superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (POD), catalyzing the decomposition of superoxide anions (O(2)(-)) and hydrogen peroxide (H(2)O(2)), while scavenging reactive oxygen species and reactive nitrogen species (RO/NS). Moreover, Fe/Mo@CM effectively alleviated inflammatory damage by inhibiting the excessive immune process and significantly reducing the number of inflammatory macrophages in the colon, thereby lowering the levels of pro-inflammatory cytokines. Furthermore, treatment with Fe/Mo@CM enhanced the expression of gut barrier proteins, which effectively mitigated DSS-induced colon shortening and histopathological damage. These findings suggest that Fe/Mo@CM can prevent oxidative stress, inflammation, and intestinal barrier disruption. Notably, Fe/Mo@CM also demonstrated potential in modulating the inflammatory microenvironment and immune process, with good gastrointestinal tolerance and strong therapeutic efficacy.