Background: Dillenia indica L. (Dilleniaceae) and Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae) are used in traditional Nigerian medicine to treat various forms of cancer. This study investigated the cytotoxic effects of these plant extracts using COV434 granulosa tumor and MCF-7 breast cancer cells. Methods: Samples of D. indica and A. leiocarpus were collected in Ibadan, Nigeria, air-dried, and extracted with methanol. Cell viability and cytotoxicity were determined using CellTiter-Glo® 2.0 assay at concentrations from 1 to 100 μg/mL. Caspase activity and apoptosis were determined using Caspase-Glo® 3/7, Caspase-Glo® 8, and ApoTox-Glo™ triplex assays, and qPCR. Autophagy was measured using a Cyto-ID Autophagy Detection Kit. Results: In COV434, aqueous partitions of A. leiocarpus root (ALR-Aq) and stem bark (ALS-Aq) had IC_50s of 23.5 and 26.7 μg/mL, respectively. In MCF-7 cells, the ALR MeOH extract had IC₅₀ of 12.75 μg/mL, while the DIS-Aq had IC₅₀ of 65.28 μg/mL. None of the extracts inhibited the growth of human osteoblasts or rat myoblasts at similar concentrations. Treatment with ALR-Aq and DIS-Aq induced mitochondrial apoptosis in MCF-7 and COV434. Both ALR-Aq and DIS-Aq induced autophagy in COV434 cells, while ALR-Aq induced autophagy in MCF-7 cells. Ellagic acid (IC₅₀ of 3.27μg/mL in COV434 cells) was isolated from ALR-Aq using bioassay-guided fractionation. Conclusion: DIS-Aq and ALR-Aq induced apoptosis in MCF-7 and COV434 cancer cells. Ellagic acid was isolated as the active constituent. Taken together, these data suggest that both plant extracts have strong anti-proliferative effects, and further investigation for their anticancer effects is warranted.