The effects of using mixed peptides (fish collagen peptides and mussel peptides) and mixed polysaccharides (Dendrobium officinale polysaccharides and Morinda officinalis polysaccharides) alone and in combination on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) were compared. UC was induced in C57/BL6 mice by allowing them to drink 3% DSS solution ad libitum for 7 days. A total of 40 mice were randomly divided into five groups: normal group, model group, peptide-treated group, polysaccharide-treated group, and combined intervention group. Combined intervention yielded the best ameliorative effect among the three types of intervention. Compared with the model group, the combined intervention group showed an 8.93% increase in body weight change rate and a 57.14% decrease in disease activity index (DAI) score. In mice in the combined intervention group, the length of the colon increased by 29.64%, while splenomegaly and hepatomegaly were reduced by 26.19% and 20.39%, respectively. The pathological score was decreased by 55.43%, and the levels of the serum inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) decreased by 24.39%, 20.69%, and 26.53%, respectively. Relative expression levels of tight junction proteins ZO-1, occludin, and claudin 1 increased by 132.61%, 79.49%, and 112.77%, respectively. All noted differences were found to be statistically significant (P<0.05). Overall, the combined use of polysaccharides and polypeptides can ameliorate DSS-induced UC in mice and prevent further deterioration due to UC. These findings provide insights into the development of health products to treat UC.