Wheat gluten was hydrolyzed by a specific enzymatic process for prepared Gln-rich wheat gluten hydrolysate(WGH), explored the regulatory effect of WGH on ulcerative colitis by dextran sulfate sodium (DSS) induced colitis model in mice. The results showed that the WGH could alleviate the weight loss and clinical symptoms of DSS-induced colitis in mice, improved the antioxidant capacity of colonic tissue and alleviate the secretion of inflammatory cytokines and the infiltration of inflammatory cells in the colonic tissue of mice. The WGH can efficiently reduce the intestinal inflammation with ulcerative colitis in mice.