A series of new substituted 3-[4-(phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives bearing groups methoxy, tert-butyl, and atoms of halogens at the para-position of the A-ring were synthesized and in vitro biological activities were evaluated as nonsugar α-glucosidase inhibitors. Most of the test compounds demonstrated significant α-glucosidase inhibitory activity relative to that of Acarbose (IC50 = 29.26 μM). The para-substitution with a methoxy group or halogens could notably increase the potency. Compounds 17, 18, and 23, with IC50 values of 0.025 μM, 0.014 μM, and 0.018 μM, respectively, may be of significance for the further development of new nonsugar α-glucosidase inhibitors.