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Homeostasis of gut microbiota is extremely essential for maintaining nutrient metabolism and regulating immunological function. The increasing evidence suggests that inflammatory bowel disease (IBD) is strongly associated with dysregulation of gut microbiota. During activated inflammation, excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by inflammatory cells play a detrimental role in regulating IBD and gut microbiota. ROS/RNS cause damage to the surrounding tissues, including nutrient absorption disorders, intestinal dysmotility and barrier dysfunction. Meanwhile, ROS/RNS provide terminal electron receptors for anaerobic respiration and support the bloom of facultative anaerobes, eventually causing gut microbiota dysbiosis. Redox-active nanoparticles (NPs) with catalytic properties or enzyme-like activities can effectively scavenge ROS/RNS, and selectively target inflamed sites via ultrasmall size-mediated enhanced permeation and retention (EPR) effect, showing great potential to regulate IBD and maintain the homeostasis of gut microbiota. In addition, the widespread application of NPs in commercial products has increased their accumulation in healthy organisms, and the biological effects on normal microbiota resulting from long-term exposure of NPs to gastrointestinal tract also need attention.