The treatment of ulcerative colitis (UC) is still an intractable medical problem. Polysaccharides are promising candidates for the treatment of UC and have received widespread attention in recent years. The objective of this study was to explore the protective effect and underlying mechanism of dandelion polysaccharide (DP) on dextran sulfate sodium (DSS)‐induced colitis in mice. Our results showed that oral administration of DP could dramatically alleviate colonic lesions, as evidenced by reduced DAI scores, shortening of colon length, and ameliorating pathologic abnormalities in colons. Additionally, the expressions of pro‐inflammatory factors (TNF‐α, IL‐1β, and IL‐6) and the infiltration of inflammation‐regulation cells, marked by myeloperoxidase and F4/80, were also inhibited after DP treatment. Moreover, DP treatment also markedly suppressed the nuclear translocation of NF‐κB‐p65 and the activation of the NLRP3 inflammasome. Furthermore, DP also activated the Nrf2/HO‐1 pathway and reduced the oxidative stress induced by DSS. Overall, these results suggest that DP could be a promising novel therapeutic approach for the treatment of UC.