In recent years,Sargassum fusiformehas gained increasing attention for its ability to improve human health and reduce the risk of disease. Nevertheless, there have been few reports on the beneficial functions of fermentedSargassumfusiforme. In this study, the role of fermentedSargassum fusiformein the mitigation of ulcerative colitis was investigated. Both fermented and unfermentedSargassum fusiformedemonstrated significant improvement in weight loss, diarrhea, bloody stools, and colon shortening in mice with acute colitis. FermentedSargassum fusiformefurther protected against goblet cell loss, decreased intestinal epithelium permeability, and enhanced the expression of tight junction proteins. FermentedSargassum fusiformereduced oxidative stress, which was demonstrated by a decrease in nitric oxide (NO), myeloperoxidase (MPO), and malondialdehyde (MDA) concentrations in the colon of mice and an increase in total superoxide dismutase (T-SOD) activity in the colon. Meanwhile, catalase (CAT) concentrations in both the colon and serum of mice were significantly increased. FermentedSargassum fusiformealso attenuated the inflammatory response, which was evidenced by the decreased level of pro-inflammatory cytokines in the colon. Moreover, fermentedSargassum fusiformeinhibited the nuclear factor-κB (NF-κB) signaling pathway and increased the production of short-chain fatty acids in the intestine. These findings indicate that fermentedSargassum fusiformemay have the potential to be developed as an alternative strategy for alleviating colitis.