Ibervillea sonorae's root, or "wareque" (Cucurbitaceae), is widely used in Mexican traditional medicine for the control of diabetes mellitus. In the present study, the hypoglycemic effects produced by the acute and chronic administration of various extracts of Ibervillea sonorae were investigated. Both the traditional preparation (aqueous decoction) and the raw extract (juice) from the root resulted in significant reductions of glycemia in healthy mice after intraperitoneal administration at a dose of 600 mg/kg. Additionally, ground dried root was used to obtain a dichloromethane (DCM) extract and a methanol (MeOH) extract. The DCM extract induced a clear reduction of glycemia in healthy (P < 0.05) and in alloxan-diabetic mice. The intraperitoneally administered DCM extract caused a severe hypoglycemia that produced lethality in all the treated animals when doses of 300 and 600 mg/kg body weight were used. Since the DCM extract showed a marked hypoglycemic activity, it was administered daily per os to alloxan diabetic rats, employing corn oil and tolbutamide as controls. After 41 days of DCM extract administration at a dose of 300 mg/kg/day, diabetic rats showed improvement in glycemia, body weight, triglycerides, and GPT in comparison with the diabetic control group. Total cholesterol, GOT, and uric acid blood levels were not affected.