The purpose of this study was to explore the protective effects of selenium containing soybean peptides (SePPs) on inflammatory bowel disease in colitis mice. During the experimental period, the mice were administered with SePPs for 14 days, and then treated with drinking water containing 2.5% dextran sodium sulfate (DSS) for 9 days, while the intervention of SePPs was continued. The results showed that low-dose SePPs (15 μg Se per kg per d bw) could effectively alleviate DSS-induced inflammatory bowel disease through the improvement of the antioxidant levels, reduction of inflammatory factor levels, and increase of tight junction protein expression of ZO-1 and occludin in the colon, thus improving the structure of the colon and strengthening the barrier function of the small intestine. Additionally, SePPs were found to significantly improve the production of short chain fatty acids (P < 0.05). Moreover, SePPs could improve intestinal microbiota diversity, significantly increasing the Firmicutes/Bacteroidetes ratio and the abundance of some beneficial genera, such as Lachnospiraceae_NK4A136_group and Lactobacillus (P < 0.05). Though high-dose SePPs (30 μg Se per kg per d bw) could improve DSS induced bowel disease, the effect was worse than that in the low-dose SePP group. These findings provide new insights into Se-containing peptides as a functional food against inflammatory bowel disease and dietary selenium supplementation.