Peptide transporters are important plasma membrane proteins that facilitate the cellular uptake of di- and tripeptides in addition to various peptidomimetic drugs. The proton-coupled oligopeptide transporter (POT) family consists of mainly four transporter proteins, which include two H(+) -coupled oligopeptide transporters known as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), along with two peptide/histidine transporters referred to as PHT1 (SLC15A4) and PHT2 (SLC15A3). These transporters play an important role in the drug delivery process in mammalian tissues. They are highly expressed in tissues such as the small intestine, kidney, liver, lung, and eye. PHT1 shows expression in immune cells, especially in B cells and plasmacytoid dendritic cells. The pathophysiological relevance of peptide transporters is emerging to be crucial in various disease conditions, e.g., PEPT1 plays a role in the physiopathology of the gastrointestinal system, particularly in IBD. Upregulated expression of peptide transporters has also been positively related to inflammatory responses. An increasing number of peptide-based drug therapies have been reported to have the potential for development of novel classes of drugs. For example, Carnosine (beta-alanyl-L-histidine) has been demonstrated to act as an antioxidant, antiglycating agent, and neuroprotector. It is transported by PEPT1 and PEPT2, facilitating its protective effects against oxidative stress in neurons and intestinal epithelial cells. Moreover, it has applications in the treatment of multidrug-resistant cancers and has been shown to improve glucose metabolism. This review gives an insight into the functional, physiological and pharmacological importance of proton-coupled oligopeptide transporter.