Abstract: In the present paper, Glycyrrhiza was selected as raw materials, and ultrasonic-assisted water bath extraction method was used to investigate crushed particle size, liquid-material ratio, ultrasonic temperature and ultrasonic time. The ultrasonic-assisted extraction technology of polysaccharide from Glycyrrhiza was optimized by Box-Behnken design methodology and the quadratic polynomial regression equation of the prediction model was established, then the antioxidant activity of the polysaccharide in vitro was determined. According to the model regression analysis, the optimum conditions were as follows: Particle size of 127 μm, liquid-material ratio of 19.32 mL/g, ultrasonic temperature of 65 ℃ and ultrasonic time of 30.2 min. Under these conditions, the yield of polysaccharide reached 10.867%. Glycyrrhiza polysaccharide showed ability to scavenge both DPPH· and ABTS⁺· with IC₅₀ values of 2.80 mg/mL and 1.96 mg/mL, respectively, and there was a certain dose-effect relationship between the scavenging rate of two different free radicals and the concentration of crude polysaccharide extract. The model established in this study can analyze and predict the yield of Glycyrrhiza polysaccharide to determine the natural antioxidant activity, which can provide an experimental basis for the development and utilization of Glycyrrhiza resources.