Phenylalanine, an amino acid, is a building block of protein. Phenylalanine is a component of food sources and also derived through supplementation. In current treatment, phenylalanine is prescribed as anti-depressant agent. The present study reviewed the possible antidepressant potential of phenylalanine. We reviewed data using the major databases, namely, Web of Science, SciFinder, Google Scholar, and PubMed. This manuscript provides a brief overview of the role of phenylalanine in depressive disorders. Phenylalanine possesses anti-depressant potential. Significant anti-depressant activities have been studied both in-vitro and in-vivo models. Based on current data, phenylalanine could be recommended as a potential candidate for clinical anti-depressant trials. Phenylalanine hydroxylase (PAH) deficiency results in intolerance to the dietetic consumption of the phenylalanine and a variety of syndromes such as deep and permanent logical disability, impaired cognitive development.