Wheat germ and fish skin usually has not been completely utilized and sometimes may be discarded, thus causing a lot of waste. Here, we aim at exploring the therapeutic anti-inflammatory effects of protease hydrolysates of wheat germ and fish skin on the ulcerative colitis (UC) mice. In the current study, wheat germ protein hydrolysates (WGPH) and fish skin gelatin hydrolysates (FSGH) treated mice had a longer colon than the DSS-induced mice. Moreover, protease hydrolysates reversed DSS-induced gut dysbiosis. Protease hydrolysates were likely to shift the balance of the intestinal flora on inflammation. In summary, these findings suggested that protease hydrolysates might serve as a latent therapy for UC treatment.