Bowman-Birk inhibitor concentrate (BBIC) is a soybean extract enriched in the Bowman-Birk inhibitor, a protein protease inhibitor. The Bowman-Birk inhibitor can inhibit proteases released from inflammation mediating cells and suppress superoxide anion radical secretion from immunocytes. This study investigates the ability of Bowman-Birk inhibitor concentrate to inhibit colon inflammation in the dextran sulfate sodium model of ulcerative colitis, an inflammatory bowel disease. When compared to mice on a standard diet, mice given food supplemented with 0.5% BBIC during and after dextran sulfate sodium treatment showed suppression of three of four scored histopathological inflammation criteria (P < 0.01), total histopathological score (P < 0.01), a 15% lower mortality rate (P < 0.01), and a delayed onset of mortality. We conclude that dietary Bowman-Birk inhibitor concentrate can beneficially affect dextran sulfate sodium-treated mice and may be useful in the treatment of human inflammatory bowel diseases, particularly ulcerative colitis.