Prolonged retention in the intestinal tract has important implications for oral medications; however, it remains highly challenging, especially in inflammatory bowel disease (IBD) therapy. The adhesion of a probiotic bacterium to the host intestinal tract can retard its transit through the gut, enhancing its effectiveness. Inspired by this property, we developed a mucoadhesive probiotic-mediated therapeutic strategy with reactive oxygen species (ROS) scavengers to achieve bioadhesion by modulating intestinal inflammation and microbiota. Bifidobacterium longum (BL), an adhesive oral probiotic, was loaded and integrated with hyaluronic acid-bilirubin nanomedicine (HABN) to produce BL@HABN. Both in vitro and in vivo, BL@HABN adhered to epithelial cells and exhibited a longer residence time to mediate more sustained release of preloaded HABN nanodrugs, to eliminate excessive ROS and protect colonic epithelial cells from ROS-mediated cytotoxicity. In addition, BL@HABN reduced the production of pro-inflammatory cytokines, induced type 2 macrophage (M2) differentiation, and promoted epithelial barrier repair. Importantly, it also restored both richness and diversity of the gut microbiota, markedly augmented the abundance of probiotics, and restrained the detrimental bacterial community. This study expands the clinical exploitation of bacteria as an adhesive carrier and enables oral nanomedicine with increased residence time and microbiota homeostasis.