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In recent years, <i>Sargassum fusiforme</i> has 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 fermented <i>Sargassum</i> fusiforme. In this study, the role of fermented <i>Sargassum fusiforme</i> in the mitigation of ulcerative colitis was investigated. Both fermented and unfermented <i>Sargassum fusiforme</i> demonstrated significant improvement in weight loss, diarrhea, bloody stools, and colon shortening in mice with acute colitis. Fermented <i>Sargassum fusiforme</i> further protected against goblet cell loss, decreased intestinal epithelium permeability, and enhanced the expression of tight junction proteins. Fermented <i>Sargassum fusiforme</i> reduced 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. Fermented <i>Sargassum fusiforme</i> also attenuated the inflammatory response, which was evidenced by the decreased level of pro-inflammatory cytokines in the colon. Moreover, fermented <i>Sargassum fusiforme</i> inhibited the nuclear factor-κB (NF-κB) signaling pathway and increased the production of short-chain fatty acids in the intestine. These findings indicate that fermented <i>Sargassum fusiforme</i> may have the potential to be developed as an alternative strategy for alleviating colitis.