The search for new drugs from natural products with bioactive properties has increased significantly in the last decade, after the drop in discoveries using chemical synthesis. Following this trend, the use of metabolomic techniques has been intensified both to discover new metabolites in complex matrices (global analysis), as well as to understand the cell's physiological changes of a specific metabolite (target analysis). Advances in the development of metabolomic technologies, as analytical techniques and bioinformatic tools, have enabled a more effective understanding of complex biological matrices, by applying analytical techniques, such as nuclear magnetic resonance, and gas and liquid chromatography coupled to mass spectrometry, thus facilitating the discovery of new bioactive compounds. Due to the complexity of metabolomics data sets, chemometric techniques have aided the identification of bioactive compounds in samples from different origins, allowing the development of new pharmaceutical products on a more rational basis. In this sense, this chapter focuses on how metabolomics has aided in the discovery of bioactive compounds using corn, propolis, and algae as biological models of study, as they have been recognized as sources of natural products with pharmaceutical potential, such as isoquinolinic alkaloids and sterols, among others. © 2022 Elsevier B.V.