ABSTRACT Oat avenanthramide‐C (AVN‐C) exhibits notable anti‐inflammatory and antioxidant properties, while its potential effects on inflammatory bowel disease (IBD) remain unclear. This study aimed to investigate the impact of AVN‐C on dextran sulfate sodium (DSS)‐induced colitis and explore the underlying mechanisms. Male C57BL/6J mice were treated with AVN‐C (5 and 10 mg/kg BW) for 1 week prior to receiving 2.5% DSS in drinking water for 7 days to induce colitis. AVN‐C treatment continued during the DSS period. The results showed that AVN‐C ameliorated DSS‐induced colitis symptoms and intestinal barrier dysfunction. AVN‐C treatment also reduced neutrophil infiltration and prevented neutrophil extracellular traps (NETs) formation. Moreover, AVN‐C elevated the relative abundance of Firmicutes and Akkermansia , while reducing Proteobacteria and Escherichia‐Shigella , thereby shifting the gut microbial composition toward a more favorable state associated with reduced inflammation. Meanwhile, AVN‐C consumption significantly enhanced intestinal immune activity and maintained gut microbiota balance by modulating primary bile acid biosynthesis through the FXR‐SHP‐NF‐κB signaling pathway. Collectively, AVN‐C exhibited a protective effect against DSS‐induced colitis by modulating neutrophil function, gut microbiota, and bile acid metabolism. These findings highlight the potential of oat AVN‐C as a therapeutic strategy for IBD, offering valuable insights into gastrointestinal health.