Background: Conventional cancer drugs have the disadvantage of severe side effects and resistance. Therefore, research targeted toward developing novel therapeutic strategies is needed. Mucuna pruriens (MP) leaf extracts have been suggested to be useful for the management of several diseases including cancer. Objective: The aim of this study was to evaluate the antioxidant and cytotoxic effect of an aqueous leaf extract of MP in different human cancer cell lines. This study also evaluated the enhanced cytotoxic effect of an aqueous leaf extract of MP with Doxorubicin (Dox) in the selected human cancer cell lines. Materials and Methods: In this study, the breast cancer cell lines (MCF-7 and MDA-MB-231), cervix carcinoma cell line (HeLa), and colon cancer cell line (HT-29) were used. As a control, the non-cancer lung cell line (MRC-5) was used. Cytotoxicity was assessed using the sulforhodamine B method. Antioxidant activity was measured with 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, 2,2-diphenyl-1-picrylhydrazyl, and ferric reducing antioxidant power assay. Results: Aqueous MP leaf exhibited cytotoxicity in all the cell lines. The highest cytotoxic activity of the test extract was observed in HeLa cells at half-maximal inhibitory concentration (IC50) = 92.8 μg/ml. Furthermore, the IC50value of the test extract when combined with Dox was significantly reduced. Specifically, in HeLa cells, the IC50was reduced by approximately 40 fold. Conclusion: This study demonstrates that aqueous MP leaf extracts could be useful as a source of antioxidants and compounds for cancer therapy. Further research is required to evaluate the chemical constituents of the leaf extracts and potential benefits for cancer therapy.