BACKGROUND: Peppermint oil has been used for centuries as a treatment for gastrointestinal ailments. It has been shown to have several effects on gastrointestinal physiology relevant to clinical care and management. AIM: To review the literature on peppermint oil regarding its metabolism, effects on gastrointestinal physiology, clinical use and efficacy, and safety. METHODS: We performed a PubMed literature search using the following terms individually or in combination: peppermint, peppermint oil, pharmacokinetics, menthol, oesophagus, stomach, small intestine, gallbladder, colon, transit, dyspepsia, nausea, abdominal pain, and irritable bowel syndrome. Full manuscripts evaluating peppermint oil that were published through 15 July 2017 were reviewed. When evaluating therapeutic indications, only randomised clinical trials were included. References from selected manuscripts were used if relevant. RESULTS: It appears that peppermint oil may have several mechanisms of action including: smooth muscle relaxation (via calcium channel blockade or direct enteric nervous system effects); visceral sensitivity modulation (via transient receptor potential cation channels); anti-microbial effects; anti-inflammatory activity; modulation of psychosocial distress. Peppermint oil has been found to affect oesophageal, gastric, small bowel, gall-bladder, and colonic physiology. It has been used to facilitate completion of colonoscopy and endoscopic retrograde cholangiopancreatography. Placebo controlled studies support its use in irritable bowel syndrome, functional dyspepsia, childhood functional abdominal pain, and post-operative nausea. Few adverse effects have been reported in peppermint oil trials. CONCLUSION: Peppermint oil is a natural product which affects physiology throughout the gastrointestinal tract, has been used successfully for several clinical disorders, and appears to have a good safety profile.