Yeasts are the most used microorganisms for biotechnological purposes. Although they have been mainly recognized for their application in the beverage and bioethanol industries, these microorganisms can be efficiently employed in pharmaceutical and food production companies. In these industrial sectors, yeasts are highly desirable for their capacity to produce bioactive compounds from simple substrates, including wastes. In this review, we present the state of the art of bioactive compound production in microbial cell factories and analyze the avenues to increase the productivity of these molecules, which benefit human and environmental health. The article addresses their vast biological activities, from preventing to treating human diseases and from pre to postharvest control on agroindustrial streams. Furthermore, different yeast species, genetically engineered or not, are herein presented not only as biofactories of the referred to compounds but also as their targets. This comprehensive analysis of the literature points out the significant roles of biodiversity, bioprospection, and genome editing tools on the microbial production of bioactive compounds and reveals the value of these approaches from the one health perspective.