The protective effects of the milk fat globule membrane (MFGM) in alleviating inflammation have been reported. However, limited attention has been paid to the key fraction of milk fat globule membrane protein (MFGMP). This study investigated the protective effects of camel MFGMP against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results revealed that administering 50 mg/kg MFGMP significantly alleviated colonic inflammation, as evidenced by a marked decrease in IL-6, IL-1β, and TNF-α levels, along with pathological damage in DSS-induced mice with UC. MFGMP supplementation partially regulated gut microbiota dysbiosis in mice with UC by increasing α-diversity and the relative abundance of beneficial gut bacteria, such as