Inflammatory bowel disease (IBD) is characterized by recurring gastrointestinal inflammation, accompanied by a significant rise in global prevalence and disease severity. The overaccumulation of reactive oxygen and nitrogen species (RONS) in the intestinal environment disrupts redox homeostasis and drives pathological overgrowth of Escherichia coli, which are central to IBD pathogenesis. Herein, we designed a multifunctional nanozyme (W-PB) to enable sustained and targeted regulation of intestinal homeostasis through dual mechanisms: specific inhibition of E. coli overgrowth during colitis and efficient RONS clearance. To ensure colon-specific delivery, W-PB was encapsulated in an electrostatically crosslinked hydrogel composed of alginate and chitosan. This formulation protects W-PB from degradation in harsh gastrointestinal conditions and releases the nanoparticles selectively under weakly alkaline intestinal pH. The released tungsten ions suppress E. coli growth via competitive displacement of molybdenum in the molybdopterin cofactor, while W-PB simultaneously neutralizes excess RONS to shield intestinal cells from oxidative damage. In DSS-induced colitis models, the W-PB gel demonstrated significant therapeutic efficacy, achieved through intestinal microbiota remodeling and oxidative stress mitigation.