Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease. Glycyrrhiza pallidiflora polysaccharide (GPP) is an important constituent of a species of Glycyrrhiza pallidiflora, but its therapeutic mechanism in UC mice is not clear. A dextran sulphate sodium salt (DSS)-induced mouse model of UC was established, and GPP was extracted by ultrasound-assisted extraction, optimised to a GPP content of 25.66% by one-factor optimisation. The effects of different doses (100, 200, 300 mg/kg) of GPP on UC were investigated. The results showed that GPP could delay the trend of weight loss, reduce the DAI score and decrease colon damage in mice, and GPP had a better ameliorative effect on enteritis, which provided a theoretical basis for studying the effect of natural products on UC.