To compare the difference of α-glucosidase inhibitory effect of total iridoid glycosides from crude products and processed products (Paozhi in Chinese) of Cornus officinalis Sieb. et Zucc. by α-glucosidase and glucose tolerance test in mice. Alcohol 40% was employed to extract the total iridoid glycosides from the crude products and the processed products then the total iridoid glycosides were enriched through macroporous resins to obtain SZY-1 and SZY-2 from the crude products and the processed products, respectively. The inhibitiory activity of these extracts was investigated on α-glucosidase inhibition in vitro and glucose tolerance test in vivo. The results demonstrated that both SZY-1 and SZY-2 were successfully enriched by macroporous resins. The contents of the total iridoid glycoside in SZY-1 and SZY-2 were 75.3% and 42.8%, respectively, and exerted inhibitory effects at various concentrations on α-glucosidase. The maximal inhibition ratio (86%) of SZY-1 was markedly higher than that of SZY-2. Meanwhile, SZY-1 was more potent than SZY-2 in decreasing blood sugar in diabetic mice induced by streptozotocin. Their effects were dependent on the dosage. In conclusion, the iridoid total glycoside from crude products and processed products of C. officinalis had α-glucosidase inhibitory effects in vitro and in vivo, and the effects of the crude products ware superior to those of processed products. It was also suggested that the hypoglycemic effects of C. officinalis may be attributable to its total iridoid glycoside.