Crohn’s disease (CD) and ulcerative colitis (UC), known as inflammatory bowel disease (IBD), are fairly common chronic inflammatory conditions of the gastrointestinal tract. Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species are produced in abnormally high levels in IBD. Their destructive effects may contribute to the initiation and/or propagation of the disease. We provided an extensive overview on the evidences from animal and human literature linking oxidative stress to IBD and its activity. Moreover, the effects of antioxidant therapy on IBD patients in randomized, controlled trials were reviewed and the need for further studies elaborated. We also summarized the evidence in support for causality of oxidative stress in IBD.