Oxidative stress is generally considered inseparable from the development and exacerbation of ulcerative colitis (UC). Therefore, reducing oxidative stress has become a possible way to alleviate UC. In this study, the therapeutic effects of different doses of liposome-embedded superoxide dismutase (L-SOD) on mice with DSS-induced UC were systematically investigated. The results showed that L-SOD significantly attenuated the signs of colitis in mice, including colonic shortening, diarrhoea, bloody stools, and histopathological changes. L-SOD ameliorated DSS-induced oxidative damage, increased SOD, catalase (CAT), and glutathione (GSH) activities, and decreased malondialdehyde (MDA) levels. In addition, L-SOD ameliorated the inflammatory response by inhibiting the expression of myeloperoxidase (MPO) and pro-inflammatory cytokines and protected barrier function by promoting the expression of the tight junction proteins occludin and ZO-1 in the colon. Importantly, the results demonstrated a bell-shaped distribution of therapeutic effects relative to the administered dose, with an optimal dose of 150 000 U kg. These results indicate that L-SOD has great potential as an ingredient in functional foods for the prevention and mitigation of UC.