Rationale: Inflammatory bowel disease (IBD) is a relapsing and idiopathic disorder. The low therapeutic efficacy of IBD urgently prompts us to seek new treatment methods. Methods and Results: In this study, we report an adipose-derived mesenchymal stem cell (AT-MSC)-based treatment strategy in which AT-MSCs specifically deliver BMP inhibitor Grem1 and anti-inflammatory factor IL-10 to inflammatory colon tissues in SETD2 deficient dextran sulfate sodium (DSS)-induced colitis mouse models. Targeted delivery of Grem1 reduced colitis by promoting intestinal stem cell regeneration and enhancing mucosal regenerative capacity. Furthermore, targeted delivery of IL-10 reduced colitis by reducing inflammatory cytokines. Conclusion: Our AT-MSCs based therapeutic strategy effectively mitigated IBD. This study has deepened our understanding of IBD therapy and provided a theoretical foundation for its clinical treatment.