Human maltase glucoamylase (MGAM) and sucrase isomaltase (SI) are two human intestinal glucosidases responsible for the final step of starch hydrolysis. MGAM and SI are anchored to the small intestinal brush border epithelial cells and contain two catalytic N-terminal and C-terminal subunits. In this study, we report the inhibition profile of 3′-O-methylponkoranol for the individual recombinant N and C terminal enzymes and compare the inhibitory activities of this compound with de-O-sulfonated ponkoranol. We show that 3′-O-methylponkoranol inhibits the different subunits to different extents, with extraordinary selectivity for C-terminal SI (K_i=7±2nM). The enzymes themselves could serve as therapeutic targets for the treatment of digestive disorders or their sequelae.