The extraction of polyphenols from opuntia milpa was prepared by ultrasound-assisted method. The optimum extraction process was determined by orthogonal experiment with the content of polyphenols and DPPH free radical scavenging rate as indicators. The antioxidant and hypolipidemic activities of polyphenol extract from opuntia milpa were evaluated. The results showed that the optimum extraction technology of opuntia milpa was solid -liquid ratio 115, ethanol concentration 65%, at 65 ℃ for 45 min. Under the control of these conditions, the content of polyphenols was 20.51 μg/mL, and DPPH clearance rate was 87.59%. The polyphenol extract of opuntia milpa has good antioxidant activity. The scavenging ability of hydroxyl radical and superoxide anion reached 93.35% and 59.83% respectively at the concentration of 10 mg/mL. The adsorption capacity of cactus polyphenol extract with cholesterol at pH 2 and 7 was (10.46±0.78) mg/g and (14.65±0.82) mg/g, respectively. At 25 mg/mL, the binding rates with sodium glycocholate and sodium taurocholate were 34.13% and 28.34%, respectively. CONCLUSION: The ultrasonic-assisted extraction process is stable and feasible, and the polyphenol extract has good antioxidant activity and hypolipidemic ability.