Abstract This paper evaluated the inhibitory effect of 3-O-[β-d-glucopyranosyl-(1→4)-β-d-glucuronopyranosyl] oleanolic acid 28-O-β-d-glucopyranosyl ester (PFS), a major saponin isolated from Polyscias fruticosa leaves, on α-amylase and α-glucosidase, and its potential for reducing the postprandial blood glucose level in mice. In enzyme inhibition assays, PFS strongly inhibited porcine pancreas α-amylase and yeast α-glucosidase. Using the Lineweaver–Burk equation, we found that PFS inhibited porcine pancreas α-amylase in a mixed noncompetitive mode, and yeast α-glucosidase via noncompetitive inhibition. In the sucrose tolerance test, PFS at 100 mg/kg body weight significantly decreased the postprandial blood glucose level in mice fed a high-sucrose diet. These findings suggest that P. fruticosa leaves and their major saponin PFS can be used to prevent and treat diabetes and its complications.