Ulcerative colitis (UC) is an idiopathic intestinal disease with an increasing incidence, and all the therapeutic drugs have different degrees of side effects. Studies have found that collagen peptide can relieve the symptoms of UC, and is safe and healthy. However, the current research is mainly limited to the prevention effect of UC, and there is still a lack of research on the therapeutic effect of UC. Eel skin is rich in collagen, but eel head is generally discarded in processing, resulting in a waste of resources. Meanwhile, there is a lack of research on eel skin collogen hydrolysates. In this study, collagen was extracted from eel skin and hydrolyzed in the hope of obtaining eel skin collagen hydrolysate (CH) with therapeutic effect on UC, so as to improve the utilization value of eel processing by-products. It was found that eel skin contained abundant collagen, accounting for 27.87% of the wet weight of the skin. The extracted collagen was of high purity and mainly type Ⅰ collagen, and eel skin could be used as a high-quality source of collagen. Collagen was enzymatically hydrolyzed to obtain eel skin collagen hydrolysate (CH) with antioxidant activity, and CH was administered to DSS induced UC mouse model. The results showed that CH could safely and healthily reduce DAI score to 0 and improve colon status in UC Model mice compared with Positive control group and Model group. Pathological sections of colon tissue showed that CH could restore the integrity of mucosal epithelium and reduce inflammatory cell infiltration. Oxidative stress index of colon tissue showed that CH could reduce MDA content (0.75 nmol/mg protein) and MPO activity (0.11 U/g tissue) in colon tissue, and improve the antioxidant capacity of colon tissue and reduce oxidative stress level by increasing GSH content (22.92 umol/g pro) and activities of SOD (693.61 U/g pro), CAT (1.69 U/g pro) and GPx (141.29 U/g pro) antioxidant enzymes, so as to treat UC.