Corn (Zea mays L.) is an important cereal crop indigenous to the Americas, where its genetic biodiversity is still preserved, especially among native populations from Mesoamerica and South America. The use of metabolomics in corn has mainly focused on understanding the potential differences of corn metabolomes under different biotic and abiotic stresses or to evaluate the influence of genetic and environmental factors. The increase of diet-linked non-communicable diseases has increased the interest to optimize the content of bioactive secondary metabolites in current corn breeding programs to produce novel functional foods. This review provides perspectives on the role of metabolomics in the characterization of health-relevant metabolites in corn biodiversity and emphasizes the integration of metabolomics in breeding strategies targeting the enrichment of phenolic bioactive metabolites such as anthocyanins in corn kernels.