Selected phenotypes of dried maca (Lepidium peruvianum) hypocotyls and supercritical CO2 extract (USPlus®) of saw palmetto (Serenoa repens) were used to determine their targeted, cytotoxic action in prostate cancer cells. Fingerprinting by HPLC-MS and PCA analysis showed compositional differences in glucosinolates, amides, macamides, and other alkaloids, which varied based on the color and the size of hypocotyls. These phytochemical differences translated into a higher antioxidant potential of red maca than black maca samples. The greatest COX-2 inhibition was demonstrated with a combination of red maca: saw palmetto (67%:33%) and red maca: saw palmetto: black maca (25%:50%:25%). The LNCaP androgen-dependent prostate cancer cell line was the most sensitive to the three-component mixture of black, red maca, and saw palmetto treatment. This combination provided the most abundant set of high-activity metabolites, and is worthy of consideration in further clinical applications and future in-depth study.