The global incidence of inflammatory bowel disease (IBD), a group of chronic gastrointestinal disorders, has been rising. The preponderance of evidence demonstrates that oxidative stress (OS) performs a critical function in the onset of IBD and the manner of its development. The purpose of this review is to outline the generation of reactive oxygen species and antioxidant defense mechanisms in the gastrointestinal tract and the role played by OS in marking the onset and development of IBD. Furthermore, the review demonstrates the various ways through which OS is related to genetic susceptibility and the mucosal immune response. The experimental results suggest that certain therapeutic regimens for IBD could have a favorable impact by scavenging free radicals, reducing cytokine and prooxidative enzyme concentrations, and improving the antioxidative capabilities of cells. However, antioxidative activity characterized by a high level of specificity may be fundamental for the development of clinical therapies and for relapsing IBD patients. Therefore, additional research is required to clarify the ways through which OS is related to the pathogenesis and progression of IBD.