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The aim of the present study was to evaluate the anti-diabetic and antioxidant potential of Coccinia grandis leaf extract. Anti-diabetic activities were evaluated via α-amylase, α-glucosidase, Protein tyrosine phosphatase (PTP 1B), and dipeptidyl peptidase-IV (DPP-IV) enzyme inhibitory assays. In addition, scavenging assay using2,2-diphenyl-1-picrylhydrazyl (DPPH), peroxynitrite (ONOO-), and total ROS was used to evaluate antioxidant potential. The MeOH extract of C. grandis exhibited the most potent inhibitory activities against α-amylase, α-glucosidase, PTP 1B and DPP-IV with the corresponding IC50 values of 8.95 ± 0.30, 4.95 ± 0.02, 1.95 ± 0.03 and 19.81 ± 0.10 µg/mL, respectively, while the MeOH extract of C. grandis showed significant antioxidant effects in DPPH, ONOO-and total ROSscavenging assay with the corresponding IC50 values of 9.71 ± 0.16, 3.95 ± 0.21and 3.43 ± 0.13 µg/mL, respectively. These results support the traditional use of C. grandis in diabetic patients, especially for the control of postprandial plasma glucose level. However, further studies on identification of the active phytochemicals acting as enzyme inhibitors and in vivo carbohydrate-digesting enzyme inhibition are required to verify its potential clinical use in diabetes mellitus. Keywords: C. grandis; α-amylase; protein tyrosine phosphatase 1B; dipeptidyl peptidase-IV (DPP-IV); α-glucosidase.