Background: An increase in prevalence of diabetes mellitus necessitates the need to develop new drugs for its effective management. Plants and their bioactive compounds are found to be an alternative therapeutic approach. Caralluma fimbriata, used in this study, is well known for its various biological effects. Objective: The present study was designed to investigate the antihyperglycemic effect of the ethanolic leaf extract of C. fimbriata. Materials and Methods: Different concentrations (1–1000 μ g/mL) of the ethanolic leaf extract of C. fimbriata were subjected to alpha-amylase and alpha-glucosidase inhibitory assay with acarbose as control. Cytotoxicity was assessed by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Glucose uptake assay was performed on L6 myotubes using the extract in 1 μ g–100 μ g/mL, using metformin and insulin as control. Results: The C. fimbriata extract showed potent inhibitory activity on enzymes of glucose metabolism in a dose-dependent manner. The maximum alpha-amylase inhibitory effect was 77.37% ± 3.23% at 1000 μ g/mL with an IC50value of 41.75 μ g/mL and alpha-glucosidase inhibitory effect was 83.05% ± 1.69% at 1000 μ g/mL with an IC50value of 66.71 μ g/mL. The maximum glucose uptake was found to be 66.32% ± 0.29% for the Caralluma extract at 100 μ g/mL and that of metformin (10 μ g/mL) was 74.44% ± 1.72% and insulin (10 μ M) 85.55% ± 1.14%. The extract was found to be safe as the IC50of extract and metformin was found to be ≥1000 μ g/mL and ≥1000 μ M, respectively, in the cell line tested. Conclusion: The study concludes that C. fimbriata has promising antihyperglycemic activity.