Taking an inhibition rate ofα-glucosidase activity as index, four factors including solid-liquid ratio, volume ratio of ethanol, time and temperature of ultrasonic treatment were selected to carry out single factor and orthogonal L9 (3⁴ ) experiments, extraction condition of Cornus officinalis Sieb. et Zucc. flesh were optimized and selected. The results show that ultrasonic treatment temperature is the most factor related to inhibition rate of ethanol extract from C. officinalis flesh toα-glucosidase. The optimization extraction condition is solid-liquid ratio 1︰15 (W ︰V), 50% ethanol (volumn ratio),ultrasonic treatment temperature 70 ℃and ultrasonic treatment time 30 min. And inhibition rate of flesh extract obtained under the optimization extraction condition is the highest (98. 5%). The hemi-inhibitory concentration (IC₅₀ ) of extract from C. officinalis flesh toα-glucosidase is 409. 30 mg·L^-1 , which is much more lower than that of the control of acarbose (890. 48 mg·L^-1 ).