Objective: Isolate and purify polysaccharides from Artemisia integrifolia and to investigate their antioxidant activity. Methods: The optimum extraction process was obtained by ultrasonic-assisted enzymatic extraction of polysaccharides from Artemisia integrifolia using response surface methodology. Results: The optimum extraction process was obtained as follows: ultrasonic power 300 W， material-liquid ratio 1∶30 g/mL， ultrasonic time 46 min， addition amount of cellulase 2.0%， addition amount of pectinase 3.0%， and under this condition， polysaccharide yield 7.67%. A total of six polysaccharide fractions were obtained by separation and purification using DEAE-52 chromatography column. Antioxidant activity studies on both AIP-2 and AIP-3 fractions showed that both AIP-2 and AIP-3 treatments at different mass concentrations had strong concentration-dependent protective effects against H2O₂-induced oxidative damage in HepG2 cells. Compared with the model group， treatment with high mass concentrations of AIP-2 and AIP-3 (50 μg/mL) increased cell survival by 54.35% and 60.26%， SOD viability increased by 35.86% and 38.98%， CAT viability increased by 173.02% and 205.42%， GSH-PX viability increased by 50.24% and 50.78%， and MDA content decreased by 46.13% and 53.87%. Conclusion: Artemisia integrifolia polysaccharide has good antioxidant activity.