Novel alpha-glucosidase inhibitors with a tetrachlorophthalimide skeleton were prepared and their structure-activity relationships were analyzed. Among them, N-phenyl-4,5,6,7-tetrachlorophthalimide (CPOP: 2) and N-(4-phenylbutyl)-4,5,6,7-tetrachlorophthalimide (CP4P: 6) showed very potent inhibitory activity, being more potent than 1-deoxynojirimycin (dNM: 1). Mechanistic studies revealed that CPOP (2) and CP4P (6) inhibit alpha-glucosidase non-competitively and competitively, respectively.