In this study, we developed calcium alginate-coated nanovesicles derived from macrophage membranes loaded with berberine (Ber@MVs-CA) for the oral treatment of ulcerative colitis (UC). Ber@MVs-CA demonstrates resistance to gastric acid and controlled drug release in the colonic pH environment, while actively targeting sites of ulcerative colitis injury. pH-responsive release of Ber in Ber@MVs-CA was confirmed through in vitro release experiments. The results indicated a total of 19.35 ± 1.61 % of Ber was cumulatively released from Ber@MVs-CA in SGF and SIF at 4 h, and approximately 87.14 ± 2.33 % release in simulated colonic fluid (pH 7.4) after 24 h. The targeting ability of Ber@MVs-CA was confirmed using laser confocal microscopy (CLSM), Transwell™ system, and in vivo imaging. Results demonstrated effective targeting of inflammatory macrophages and sustained retention in the colon. In vitro and in vivo (mice) assessments via immunofluorescence, ELISA kit, and reactive oxygen species (ROS) assays demonstrated that Ber@MVs-CA effectively attenuated inflammatory responses, modulated macrophage polarization, and inhibited oxidative stress. Additionally, we evaluated the therapeutic efficacy of Ber@MVs-CA in a Clostridium perfringens-induced enteritis model in chickens, demonstrating its effectiveness in alleviating enteritis. Consequently, Ber@MVs-CA exhibits great potential as an oral nano-formulation for the treatment of enteritis. Thus, Ber@MVs-CA shows great potential as an oral nano-formulation for the treatment of enteritis.