To study potential inhibitory molecules of Saccharomyces cerevisiae α-glucosidase, a new homology model based on the most recent crystal structure of Saccharomyces cerevisiae isomaltase (PDB: 3A47) was built. This newest model was used to dock five known natural α-glucosidase inhibitors to explore the putative allosteric drug binding pockets. Examination of the docking simulations and in silico mutagenesis revealed a potential druggable pocket for binding and a critical lysine residue making thermodynamically favorable binding with the inhibitors. In order to support the data analyzed from the docking simulation a series of inhibition assays were conducted.