During the last few years, numerous attempts were made to identify effective α-glucosidase inhibitors from natural sources in order to develop new alternatives for diabetes management. Smallanthus sonchifolius (yacon) leaves were found to be effective in controlling postprandial hyperglycemia. Enhydrin, a constituent of yacon leaves, was noted for its significant hypoglycemic properties in diabetic rats. These properties were also demonstrated for yacon leaves decoction, which is rich in phenolic compounds such as chlorogenic acid and its derivatives. The purpose of the present study was to evaluate the potential of yacon leaves decoction and the isolated compound enhydrin to inhibit α-glucosidase enzyme, a possible mechanism of the above antihyperglycemic effect. In vitro assays showed that both 10% decoction and enhydrin significantly inhibited the activity of the yeast α-glucosidase enzyme in a dose-dependent manner, IC values being 50.40 and 134.17 μg/ml, respectively. In vivo experiments showed a rapid decrease in the hyperglycemic peak after sucrose load (2 g/kg body weight) in normal rats treated with the 10% decoction (140 mg/kg) and enhydrin (0.8 mg/kg). Both treatments caused a significant decrease in blood glucose levels in diabetic rats after sucrose load compared to diabetic control. These results suggest that both products assayed could be effective in the management of postprandial hyperglycemia through inhibition of α-glucosidase in the small intestine.