Context: Hyperglycemia is the hallmark of type 2 diabetes mellitus, and its prevention will go a long way in managing the disease and its associated complications. Reduction of postprandial hyperglycemia through retarding carbohydrates digesting enzymes is one of the major therapeutic approaches used in the management of diabetes. Objective: The aim of the present study was to investigate the antidiabetic and cytotoxic effects of Cissus cornifolia extracts in vitro. Materials and Methods: The α-amylase and α-glucosidase inhibitory activities of ethanolic and aqueous extracts of C. cornifolia root and leaves were investigated when the cytotoxic effects of these extracts were analyzed using MTT assay on human embryonic kidney (HEK 293) cell lines. Results: The root ethanolic extract showed a mild α-amylase inhibitory activity with IC50value of 22.75 ± 1.23 μg/ml, but strong α-glucosidase inhibitory activity with IC50value 2.81 ± 0.97 μg/ml and the aqueous root extract indicated moderate inhibition for both α-amylase and α-glucosidase with IC50values of 33.70 ± 3.75 and 37.48 ± 2.35 μg/ml, respectively. The ethanolic root extract was found nontoxic at tested concentrations on HEK 293 cell lines as confirmed by the MTT assay with 93% cell viability at the highest concentration (200 μg/ml) tested. However, the aqueous extracts (leaf and root) were found cytotoxic at concentrations above 50 μg/ml. Conclusion: Data of this study suggest that the root ethanolic extracts of C. cornifolia possesses moderate α-amylase, but strong α-glucosidase inhibitory activity in vitro and did not show significant cytotoxicity with the tested concentrations.