Objective: This study aimed to explore the potential use of honey peach kernel as a by-product of characteristic agricultural product processing. Methods: The processing technology was optimized based on a single factor test and response surface test by analyzing the effects of enzyme addition amount, ultrasonic temperature, ethanol concentration, and ultrasonic time on the extraction amount of peach kernel polyphenols. Additionally, the antioxidant activities of the extracted polyphenols were studied. Results: The results showed that the optimal extraction parameters were as follows: enzyme adding quantity 5%, ultrasonic temperature 63 ℃, ethanol concentration 60%, and ultrasonic time 37 min. Under this condition, the extraction amount of polyphenols was 8.63 mg/g. The antioxidant results showed that the scavenging rates of ABTS free radical, DPPH free radical, OH free radical, and O^-₂ free radical were 75.22%, 85.91%, 44.72%, and 45.76%, respectively. The IC₅₀ of the four free radicals were 0.099, 0.098, 0.332, and 0.320 mg/mL, respectively. Conclusion: The approach of ultrasonic-assisted enzymolysis can effectively extract the polyphenols in the honey peach kernel, the polyphenols of the honey peach kernel had good antioxidant activity.