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Oral mucositis is a common and frequentoccurring disease and there is no effective treatment. In this study, we investigated the efficacy of polyphenolic extract from Artemisia selengensis Turcz (PPAST) in the prevention and treatment of oral mucositis. Cultured human gingival fibroblast cell HGF-1 was used as an in vitro experimental model to confirm the effect of PPAST inhibition of lipopolysaccharide(LPS) on cytotoxicity and its effect on the production of inflammatory cytokines. A rat model of oral ulcer was induced by acetic acid cauterization, and the curative effect of PPAST on oral ulcer was investigated from ulcer area and ulcer duration. PPAST significantly inhibited the toxic effect of LPS on HGF1 cells, improved the survival rate of HGF1 cells, and showed a concentration-dependent inhibition of TNF-α in HGF-1 cell. Treatment with PPAST reduced mucositis scores, promoted oral ulcer healing, and reduced plasma TNF-α levels in rats. Experimental data show that PPAST is safe and effective in the prevention and treatment of oral inflammatory diseases.