Ulcerative colitis (UC) is a type of inflammatory bowel disease and is considered a chronic gastrointestinal disorder. Igongsan (IGS) is a Korean herbal medicine, which has been used to treat digestive disorders. However, the ameliorative effect and molecular mechanisms of IGS in intestinal inflammation have not yet been studied in detail. The present study aimed to investigate the protective effects of IGS and its constituent, ergosterol, in a mouse model of dextran sulfate sodium (DSS)‑induced colitis. Colitis was induced in mice by supplementing their drinking water with 5% (w/v) DSS for 7 days. The effects of IGS were then determined on DSS‑induced clinical signs of colitis, including weight loss, colon shortening, diarrhea and obscure/gross bleeding. In addition, the effects of IGS were determined on the expression levels of inflammation‑associated genes in the colon tissue of DSS‑treated mice. The results of the present study demonstrated that mice treated with DSS exhibited marked clinical symptoms, including weight loss and reduced colon length. Treatment with IGS attenuated these symptoms and also suppressed the expression levels of tumor necrosis factor‑α and interleukin‑6, as well as the expression of cyclooxygenase‑2 in the colon tissue of DSS‑treated mice. IGS also reduced the activation of the transcription factor nuclear factor‑κB p65 in the colon tissue of DSS‑treated mice. In addition, ergosterol was shown to attenuate the DSS‑induced clinical symptoms of colitis in mice. In conclusion, the present study provided experimental evidence that IGS may be a useful therapeutic drug for patients with UC.