Use of α-glucosidase inhibitorsisone of the therapeutic approaches for decreasing postprandial hyperglycemia. Sulochrin (1) from Aspergillusterreusas well as twosynthetic sulochrinderivatives were assessed for antidiabeticactivity against yeast and rat intestine α-glucosidase. Sulochrin showed potential inhibition against yeast α-glucosidase, through a non-competitivemode with an IC50value of 133.79 μM, and rat intestineα-glucosidase by uncompetitive mode with an IC50value of 144.59 μM.. Twosynthetic derivatives of sulochrinwere also preparedby brominationwhich resultedindibromo-sulochrin(2) and tribromo-sulochrin(3). Preliminary SAR studies of sulochrinderivatives revealed that the yeast α-glucosidase inhibitory activity of compound 2and 3increased than 1due to substitution of hydrogen atom with bromine with IC50values of 122.65 and 49.08 μM, respectively.However, the inhibitory activity against rat intestine α-glucosidase of 2and 3wasdecreased comparedto 1.To the best our knowledge, this is the first report of structure-activity relationship of sulochrinand its derivatives as α-glucosidase inhibitors. These results suggested that sulochrincan potentiallybe used as a lead compound to develop new α-glucosidase inhibitorfrom microorganisms.