Objective To investigate of the preparation technology of peanut α-glucosidase inhibitory activity peptide with ultrasonic wave assisted enzymatic hydrolysis reaction. Methods The cold pressed peanut protein powder was used as raw material, the substrate concentration, pH value, enzyme dosage, temperature, time and ultrasonic power were used as investigation factors, and the α-glucosidase inhibitory rate was used as the index. On the basis of single factor experiment, the process was optimized by response surface methodology and Box-Benhnken design. Results The optimum preparation process of α-glucosidase inhibitory activity peptide complex with ultrasonic wave assisted enzymatic hydrolysis reaction were the substrate concentration of 11.13%, pH value of 9.45, enzyme dosage of 1.2%, temperature of 42 ℃, time of 44 min, and ultrasonic power of 1200 W. The model predictive inhibitory rate under these process conditions was 91.07%. The inhibitory rate of verification experiment was (88.70±0.63)%, and the difference between the predicted value and the experimental value was 2.60%. The model was fitted well with the actual situation and the correctness of the proposed model was verified. Conclusion Therefore, the response surface method is feasible for the preparation parameter optimization of peanut α-glucosidase inhibitory activity peptide and the obtained technological conditions have practical application values.