This study was designed to investigate whether diphlorethohydroxycarmalol (DPHC) may inhibit alpha-glucosidase and alpha-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. DPHC isolated from Ishige okamurae, a brown algae, evidenced prominent inhibitory effect against alpha-glucosidase and alpha-amylase. The IC(50) values of DPHC against alpha-glucosidase and alpha-amylase were 0.16 and 0.53 mM, respectively, which evidenced the higher activities than that of acarbose. DPHC did not exert any cytotoxic effect in human umbilical vein endothelial cells (HUVECs) at various concentrations (from 0.49 to 3.91 mM). The increase of postprandial blood glucose levels were significantly suppressed in the DPHC-administered group than those in the streptozotocin-induced diabetic or normal mice. Moreover, the area under curve (AUC) was significantly reduced via DPHC administration (2022 versus 2210 mmol x min/l) in the diabetic mice as well as it delays absorption of dietary carbohydrates. Therefore, these result indicated that DPHC might be a potent inhibitor for alpha-glucosidase and alpha-amylase.