Abstract  Dietary proteins are cleaved within the intestinal lumen to oligopeptides which are further processed to small peptides (di‐ and tripeptides) and free amino acids. While the transport of amino acids is mediated by several specific amino acid transporters, the proton‐coupled uptake of the more than 8000 different di‐ and tripeptides is performed by the high‐capacity/low‐affinity peptide transporter isoform PEPT1 (SLC15A1). Its wide substrate tolerance also allows the transport of a repertoire of structurally closely related compounds and drugs, which explains their high oral bioavailability and brings PEPT1 into focus of medical and pharmaceutical approaches. Although first evidence for the interplay of nutrient supply and PEPT1 expression and function had been described over 20 years ago, many aspects of the molecular processes controlling its transcription and translation and modifying its transporter properties are still awaiting discovery. The present review summarizes the recent knowledge about factors modulating PEPT1 expression and function in C. elegans, D. rerio, M. musculus and H. sapiens with focus on dietary ingredients, transcription factors and functional modulators like the sodium‐proton exchanger NHE3 and selected scaffold proteins. This article is protected by copyright. All rights reserved