To keep blood glucose levels as close to normal as possible is the major goal of diabetes mellitus treatment $alpha$-Glucosidase is the enzyme that digests die1my carbohydrate and inhibition of this enzyme may suppress postprandial hyperglycemia. The methanol extract of Polygonum multiflorum Thunberg was tested for inhibitoty activity against $alpha$-glucosidase in vitro and in vivo. Polygonum multiflorum Thunberg extract inhibited yeast $alpha$-glucosidase activity in a concentration-dependent manner. Polygonum multiflorum Thunberg showed an $IC_{50}$ value of 0.48 mg/mL. The ability of Polygonum multiflorum Thunberg extract to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without the methanol extract of Polygonum multiflorum Thunberg extract (500 mg/kg) was administered to diabetic rats by gastric intubation after an overnight fast A single oral dose of Polygonum multiflorum Thunberg extract significantly inhibited increases in blood glucose levels at 60 and 90 min (p<0.05) and significantly decreased incremental response areas under the glycemic response curve (p<0.05). These results suggest that Polygonum multiflorum Thunberg may have an antihyperglycemic effect by inhibiting $alpha$-glucosidase activity in the animal model of diabetes mellitus.