Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal (GI) disorder associated with abdominal pain and change in bowel habits that its etiology is not known yet. In the recent years, melatonin has been proposed as a possible candidate. In the present work, all clinical or non-clinical data about effects of melatonin in GI tract and IBS obtained from literature without time limit up to August 2010 have been studied and reviewed. Eight clinical trials were reviewed for efficacy and disturbance of melatonin in IBS and other GI disorders. The results showed disturbances in endogenous melatonin concentration in IBS patients and significant benefits of exogenous melatonin in these patients by decreasing abdominal pain and improvement of overall IBS symptom scores. The results of seventeen non-clinical studies showed anxiolytic, anti-inflammatory, anti oxidative and motility regulatory effects of melatonin on GI tract. In conclusion melatonin can be a target of interest in IBS because of its potentials to regulate GI motility.