Inflammatory bowel diseases (IBDs) are chronic autoimmune disorders with a rising global prevalence, often associated with increased levels of reactive oxygen species (ROS) and disruptions in the intestinal microbiome. Here, we developed a superior armored probiotic with colon-targeting and ROS scavenging capacities by sequentially coating probiotics with MnO₂ nanozyme and colon-responsive degradation material. This versatile encapsulation technique enhances the efficacy of bacterial therapy while preserving probiotic viability and ensuring ultra-resistance to extreme environmental stress. A key advantage is the timely “awakening” of probiotics through pH and ROS-responsive degradation in the inflamed colon, facilitating effective treatment. This approach is beneficial for the prophylactic and therapeutic management of IBDs, aiding in inflammation relief, colonic epithelial barrier repair, and gut microbiota modulation. This study offers a novel therapeutic strategy against colitis and underscores the potential of armored probiotics for treating other inflammatory diseases.