The species Chenopodium quinoa Willd. and Amaranthus hybridus L. are Andean staples, part of the traditional diet and gastronomy of the people of the highlands of Colombia, Ecuador, Peru, Bolivia, northern Argentina and Chile, with several ethnopharmacological uses, among them anticancer applications. This review aims to present updated information on the nutritional composition, phytochemistry, and antimicrobial and anticancer activity of Quinoa and Amaranth. Both species contribute to food security due to their essential amino acid contents, which are higher than those of most staples. It is highlighted that the biological activity, especially the antimicrobial activity in C. quinoa, and the anticancer activity in both species is related to the presence of phytochemicals present mostly in leaves and seeds. The biological activity of both species is consistent with their phytochemical composition, with phenolic acids, flavonoids, carotenoids, alkaloids, terpenoids, saponins and peptides being the main compound families of interest. Extracts of different plant organs of both species and peptide fractions have shown in vitro and, to a lesser degree, in vivo activity against a variety of bacteria and cancer cell lines. These findings confirm the antimicrobial and anticancer activity of both species, C. quinoa having more reported activity than A. hybridus through different compounds and mechanisms.