In recent decades, the use of plants as a natural remedy has been widely applied in traditional medicine and the treatment of various diseases, including cancer. However, in order to confirm the potential benefits of anticancer drug development from natural sources, in-depth screening assessments are necessary. In the present study, we aimed to evaluate the cytotoxic effects of eight medicinal plants against breast carcinoma and hepatocellular carcinoma cell lines. Remarkably, among all the tested plant extracts, Pyracantha angustifolia and Paullinia cupana extracts showed maximum inhibition in the two cancer cell line models, as detected by cell viability assays, but not in normal mammary epithelial cells. Moreover, induction of cell cycle arrest was seen in both cancer cell models after treatment with extracts derived from the fruits of P. angustifolia and the seeds of P. cupana. Phytochemical and antioxidant analyses demonstrated the presence of high phenolic and flavonoid contents, including an increase in 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity. The growth inhibition of human breast carcinoma and hepatocellular carcinoma cells mediated by both extracts appears to be associated with apoptosis and upregulated expression of pro-apoptotic genes (caspase-3, caspase-7, tumor suppressor protein-p53, cytochrome c, poly (ADP-ribose) polymerase, p53 upregulated modulator of apoptosis, and Bcl-2-associated X-protein). Together, these results indicate that P. angustifolia and P. cupana offer a promising approach for the development of anticancer agents. However, further detailed research is required to make these plants applicable for therapeutic use.