Objective To study the extraction process and in vitro activity of polysaccharide from Musella lasiocarpa.Methods Ultrasonic-assisted ionic liquid extraction is adopted. With the extraction rate of polysaccharide as the evaluation index, single factor and response surface methods are used to optimize the extraction process of polysaccharide. Furthermore, the polysaccharide is characterized in terms of the antioxidant activity, monosaccharide composition, and inhibitory activities on pancreatic lipase and α-amylase.Results The extraction process of polysaccharide is optimized as follows: extraction power of 200 W, ionic liquid volume of 1.80 mL, ultrasonic time of 32 min, solid-liquid ratio of 1:36, and ultrasonic temperature of 37 ℃, under which the extraction rate of polysaccharide is (32.20±0.68) mg/g. HPLC shows that the monosaccharides of the purified polysaccharide include mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and arabinose, with the ratio of 1.26∶6.37∶4.29∶0.86∶0.72∶22.35∶0.21∶2.46∶0.18. The scavenging rates against DPPH·, ·OH, ABTS⁺·, and O2-· and the inhibition rates on pancreatic lipase and α-amylase of polysaccharide increase with the increase in mass concentration. When the mass concentration of polysaccharide is 5.0 mg/mL, the scavenging rates against DPPH·, ·OH, ABTS⁺·, and O2-· are 78.60%, 67.70%, 79.85%, and 69.67%, respectively. The IC₅₀ values show that the scavenging abilities of the polysaccharide against free radicals follow the trend of DPPH·>ABTS⁺·>·OH>O2-·. The polysaccharide at the mass concentration of 10 mg/mL shows the inhibition rates of 67.2% and 58.3% on pancreatic lipase and α-amylase, respectively.Conclusion The ultrasonic-assisted ionic liquid method for extracting polysaccharide from M. lasiocarp has the advantages of high extraction yield and good in vitro activity. This method demonstrates good application prospects and great potential in the extraction of active substances from natural products.