In this study, a rat model of ulcerative colitis (UC) induced by sodium dextran sulfate (DSS) was used to investigate the ameliorative effect of casein glycomacropeptide (CGMP) on colitis. The results showed that CGMP improved the growth performance and reduced the disease activity index (DAI) of UC rats. Mechanistic studies revealed that CGMP improved intestinal permeability by reducing the degree of inflammatory infiltration in the colon tissue and the levels of the inflammatory factors TNF-α and IL-6, thereby alleviating colon tissue damage caused by DSS. At the same time, it protected the intestinal mucosal barrier and alleviated the symptoms of enteritis by regulating the production of short-chain fatty acids by the intestinal flora