Abstract: The alkaline degradation on red raspberry seed high polymeric proanthocyanidins was optimized by response surface methodology The hypoglycemic enzyme inhibitory ability of high polymeric polyproanthocyanidins and oligomeric procyanidins were evaluated in this research. Based on single-factor test, average polymerization degree of proanthocyanidins was taken as index. Alkaline degradation conditions of high polymeric proanthocyanidins were optimized by Box-Behnken of response surface experiment. And the inhibition effect on α-glucosidase and α-amylase ability of high polymeric polyproanthocyanidins and oligomeric procyanidins were evaluated while inhibition rate was taken as index. The results showed that alkali concentration 2.13%, solid-liquid ratio 1:10.25 (mg/mL), Degradation time 42 min, degradation temperature 60℃ made the average polymerization degree of proanthocyanidins dropped from 5.44 to 2.14±0.11.The IC₅₀ values of α-glucosidase for high polymeric polyproanthocyanidins and oligomeric procyanidins were 0.730 and 0.291 mg/mL, and their IC₅₀ for α-amylase were 0.578 and 0.342 mg/mL, respectively. The degradation products of high polymeric proanthocyanidins showed a good inhibitory effect on α-glucosidase and α-amylase. And the activity was higher than that of high polymeric polyproanthocyanidins. Thus oligomeric proanthocyanidins have good hypoglycemic activity and are a natural herb with potential hypoglycemic activities.