The control of blood glucose levels is critical in the treatment of diabetes mellitus. α-Glucosidase inhibitors are of great importance in reducing hyperglycemia, and plants have provided many of these agents. The present study aimed at investigating the effect of two stilbenes, lonchocarpene and 3,5-dimethoxy-4'-O-prenyl-trans-stilbene (DPS), isolated from the Amazonian plant Deguelia rufescens var. urucu, on α-glucosidase activity and on mice postprandial hyperglycemia. Lonchocarpene and DPS inhibited α-glucosidase in vitro, with pIC(50) values of 5.68 ± 0.12 and 5.73 ± 0.08, respectively. In addition, when given orally, DPS produced a significant reduction of hyperglycemia induced by an oral tolerance test, while lonchocarpene did not. Data suggest that DPS may have a potential use as an antidiabetic drug.