ABSTRACTObjective: This research investigated in vitro hypoglycemic and antimicrobial activity of methanolic fruit extract of Cucumis callosus (MECC) (Rottl.)cogn.Methods: The in vitro antidiabetic ability of MECC was evaluated by inhibition studies of the digestive enzymes including α-amylase and α-glycosidase.The antimicrobial activity of extract was further evaluated against 21 laboratory strains belongs to 8 bacterial species and 4 fungal species using cupplateagardiffusion assayand agardilution assay.Results: Our assay result suggested that the MECC exhibited dose-dependent increase in percentage inhibitory activity on α-glycosidase(IC50 405.37 µg/ml) and α-amylase enzymes (IC721.55 µg/ml). The results of antimicrobial activity also showed that the extract inhibited the growthof 13 strains of 7 bacterial species and all fungal species.50 Conclusion: The observed inhibitions of α-amylase and α-glycosidase and inhibition of some microbial species suggested that the MECC may be usefulin the management of diabetes mellitus and treatment of some infectious diseases.Keywords: Cucumis callosus, Diabetes, α-amylase, α-glycosidase, Antimicrobial