© 2023New curative and preventative approaches with high therapeutic efficacy and minimal side effects are needed for many forms of cancer. Therefore, the current study aimed to assess the cytotoxic and antioxidant capacity of Smilax excelsa and Aegopodium podagraria, which are consumed on a daily diet in the Black Sea region of Turkiye, as well as their phytochemical composition to pinpoint the compounds responsible for these activities. The effects of the treatments on human prostate (PC3), colorectal (HCT116), and lung (A549) carcinoma cell survival and free radical scavenging potentials were investigated. Total phenolic and flavonoid contents and significant phenolic compounds were detected and quantified by HPLC. The extracts reduced cell viability in all cancer cells in a dose-dependent manner, while the most potent cytotoxic effects were noted on PC3 cells. S. excelsa inhibited cell growth on PC3 cells at both lower and higher concentrations (50–1000 μg/mL) compared with the control (p < 0.05). S. excelsa methanol extract exhibited the strongest ABTS and DPPH free radical scavenging capacities, with the IC50 values of 17.16 and 45.81 μg/mL, respectively. The highest amounts of total phenolics and flavonoids, as well as chlorogenic acid and caffeic acid, were also observed in S. excelsa methanol extract. Our results suggest that S. excelsa and A. podagraria, along with the isolated compounds, may contribute to the treatment of prostate cancer. To the best of our knowledge, this is the first study analyzing the impacts of these plants on PC3, HCT116, and A549 cells.