Aminocyclitols have been recognized as a-glucosidase inhibitors due to their close structural relationship with sugar. The inhibitory effect can be improved by modifying the cyclic core and Nsubstituted moiety. In the present investigation, a series of new N-alkyl and N-acyl aminoquercitols have been synthesized using a natural chiral building block, (+)-proto-quercitol, and evaluated for aglucosidase inhibition. N-Alkyl aminoquercitols encompassing medium alkyl chains (hexyl to decyl chains) showed highly improved inhibition against rat intestinal maltase, 3–6 fold more potent than antidiabetic drug acarbose. Kinetic study of potent N-substituted aminoquercitols indicated that they retarded maltase function in a competitive manner.