Peptides have vast potential as tools for biological processes, as probes to diagnose diseases, and as treatments for a broad range of human diseases. They are characterised by high potency, specificity for their target receptor and low toxicity. Despite their advantages, peptides’ low oral bioavailability hinders their potential in biological applications. Recently, we have synthesised a series of peptide analogues conjugated to lipid tags and shown to display oral bioavailability; the molecular details on how this molecular tag increases oral bioavailability is not understood. Using a variety of biophysical techniques with model membranes and tissues, we are investigating the molecular mechanism used by lipid tagged peptides to cross cell membranes, and intestinal epithelial cells. in vitro studies will be compared with in vivo bioavailability and efficacy to understand the mechanism behind the dramatic increase in oral bioavailability. This project is focused on making orally bioavailable peptides that can provide a therapeutic alternative to treat cancer and other diseases.