Inflammation and oxidative process are associated with inflammatory bowel disease (IBD). Regarding anti-inflammatory and antioxidant potentials, melatonin has been found beneficial in several experimental and clinical studies including inflammatory bowel disease (IBD). Our objective in this study is to review and evaluate all non-clinical and clinical studies on the efficacy of melatonin in IBD. All indexing databases were searched for inflammatory bowel disease' and 'melatonin' keywords, without time limit up to May 2011. Three clinical trials and fifteen non-clinical studies are reviewed and analyzed. The majority of these studies indicate that melatonin has a positive impact on IBD with no or negligible side effects. Such results have been mostly explained through free radical scavenging and diminishing inflammation. It is yet crucial to determine the efficacy of melatonin in combination with other established drugs in more clinical trials, not only for further confirmation of its efficacy, but also to investigate its possible side effects in longer durations of therapy.