Inflammatory bowel disease (IBD) is a severe chronic intestinal disorder with a rising global incidence. Current therapies, including the delivery of anti-inflammatory drugs and probiotics, face significant challenges in terms of safety, stability, and efficacy. In IBD patients, the activity of antioxidant enzymes (, superoxide dismutase, glutathione peroxidase, and glutathione reductase) is reduced at the site of intestinal inflammation, leading to the accumulation of reactive oxygen species (ROS). This accumulation damages the intestinal mucosa, disrupts tight junctions between cells, and compromises the integrity of the intestinal barrier, exacerbating IBD symptoms. Therefore, nanoparticles responsive to ROS and capable of mimicking antioxidant enzyme activity, such as boronates, polydopamine, sulfides, and metal nanozymes, have emerged as promising tools. These nanoparticles can respond to elevated ROS levels in inflamed intestinal regions and release drugs to effectively neutralize ROS, making them ideal candidates for IBD treatment. This review discusses the application of various ROS-responsive nanomaterial delivery systems in IBD therapy, highlights current challenges, and outlines future research directions. Furthermore, we explore the "layered programmable delivery" strategy, which combines ROS-responsive nanoparticles with pH-responsive and cell membrane-targeted nanoparticles. This strategy has the potential to overcome the limitations of single-mechanism targeted drug delivery, enabling multi-range and multi-functional treatment approaches that significantly enhance delivery efficiency, providing new insights for the future of localized IBD treatment.