An extract (100 mg/kg) of the stem bark of Hintonia standleyana caused a significant decrease in blood glucose levels in both normal and streptozotocin (STZ)-diabetic rats when compared with vehicle-treated groups (p < 0.05). From the active extract, 3- O- beta- D-glucopyranosyl-23,24-dihydrocucurbitacin F ( 1), 5- O-beta- D-glucopyranosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin ( 2) and 5- O-[ beta- D-apiofuranosyl-(1-->6)- beta- D-glucopyranosyl]-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin ( 3) were isolated. Coumarin 3 is a new natural product and was identified by spectroscopic methods. Compounds 1 and 3 did not decrease blood glucose levels in normal rats. However, in two different long-term subacute experiments, using animals with a developing diabetes condition and with STZ-induced diabetes, both compounds at daily doses of 10 mg/kg (developing diabetes condition) or 30 mg/kg (STZ-induced diabetes condition) provoked a significant antihyperglycemic activity (p < 0.05). Furthermore, compound 3 restored normal blood glucose levels in STZ-induced diabetic rats. In all cases, the groups treated with the active principles and the extract showed less body weight lost than the glibenclamide-treated and diabetic control groups (p < 0.05). These results showed that the antihyperglycemic active principles of H. standleyana are both 4-phenylcoumarins and cucurbitacin glycosides.