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Previous studies have demonstrated that the intestinal abundance of <i>Bacteroides uniformis</i> is significantly higher in healthy controls than that in patients with ulcerative colitis (UC). However, what effect <i>B. uniformis</i> has on the development of UC has not been characterized. Here, we show for the first time that <i>B. uniformis</i> F18-22, an alginate-fermenting bacterium isolated from the healthy human colon, protects against dextran-sulfate-sodium (DSS)-induced UC in mice. Specifically, oral intake of <i>B. uniformis</i> F18-22 alleviated colon contraction, improved intestinal bleeding and attenuated mucosal damage in diseased mice. Additionally, <i>B. uniformis</i> F18-22 improved gut dysbiosis in UC mice by increasing the abundance of anti-inflammatory acetate-producing bacterium <i>Eubacterium siraeum</i> and decreasing the amount of pro-inflammatory pathogenetic bacteria <i>Escherichia-Shigella</i> spp. Moreover, <i>B. uniformis</i> F18-22 was well-tolerated in mice and showed no oral toxicity after repeated daily administration for 28 consecutive days. Taken together, our study illustrates that <i>B. uniformis</i> F18-22 is a safe and novel probiotic bacterium for the treatment of UC from the healthy human colon.