Inflammation is a key driver of intestinal inflammatory diseases, such as inflammatory bowel disease (IBD). While biologics have demonstrated notable success in treating some patients, there remains a critical need for alternative therapeutic strategies to address primary and secondary non-responders. In this study, a dendritic cell (DC)-based biohybrid immunomodulator is developed to alleviate intestinal inflammation, demonstrating remarkable efficacy in combating IBD. This biohybrid immunomodulator is engineered by conjugating resolvin E1-loaded liposomes with Fas ligand (FasL)-transfected DCs. Elevated Fas expression is observed in intestinal tissue samples from IBD patients, and the immunomodulator effectively reduced inflammation by selectively eliminating Fas(+)CD8(+) T cells and neutrophils. The therapeutic potential of this approach is validated in both mouse and rabbit models of IBD, where it exhibites significant anti-inflammatory effects. Furthermore, the immunomodulator can be manufactured using human peripheral blood mononuclear cells and bone marrow-derived DCs, demonstrating a robust capacity to induce T cell apoptosis. This study presents a feasible and customizable strategy for mitigating intestinal inflammation, offering a promising advancement in the treatment of IBD.