The etiology of inflammatory bowel disease (IBD) is extremely complex and related to an excessive immune response that results in the pathologically release of reactive oxygen species (ROS) via tissue injury and chronic inflammation. Generally, excessive ROS production is one of the essential mediators for inflammatory pathogenesis. Targeting cumulate ROS to interrupt pathological inflammatory responses has been recognized as a feasible strategy for inflammatory suppression of IBD. Correspondingly, the overexpression of ROS can also trigger the drug release of novel drug delivery systems to alleviate IBD symptoms. In this review, we summarized the pathological production of endogenous ROS in IBD, discussed the enormous potential of multiple kinds of ROS-scavenging and ROS-triggering novel delivery systems for the treatment of IBD, including enzymology, metal, polyphenols, natural pigments, nitroxide radicals-contained and sulfide-loaded drug delivery systems, and other novel ROS-responsive materials to synthesize ROS-based drug delivery systems. We also summarized the immunomodulatory effects of ROS-targeted drug delivery systems for the treatment of IBD. Besides, based on the requirements of clinical applications and industrialization development, the challenges faced in the evolution of redox drug delivery systems were also discussed. Collectively, this review provides a reliable reference to the development of ROS-scavenging and ROS-triggering drug delivery systems for the medical intervention of IBD.