Inflammatory bowel disease (IBD) is a type of chronic recurrent inflammation disease that mainly includes Crohn's disease and ulcerative colitis. Currently, the treatments for IBD remain highly challenging, with clinical treatment drugs showing limited efficacy and adverse side effects. Thus, developing drug candidates with comprehensive therapeutic effects, high efficiency, and low toxicity is urgently needed. Recently, micro/nanomaterials have attracted considerable interest because of their bioavailability, multitarget and efficient effects on IBD. In addition, gut modulation plays a substantial role in restoring intestinal homeostasis. Therefore, efficient microbiota-based strategies modulating gut microenvironment have great potential in remarkably treating IBD. With the development of micro- and nanomaterials for the treatment of IBD and more in-depth studies of their therapeutic mechanisms, it has been found that these treatments also have a tendency to positively regulate the intestinal flora, resulting in an increase in the beneficial flora and a decrease in the level of pathogenic bacteria, thus regulating the composition of the intestinal flora to a normal state. In this review, we first present the interactions among the immune system, intestinal barrier, and gut microbiome. In addition, recent advances in administration routes and methods that positively arouse the regulation of intestinal flora for IBD using probiotics, prebiotics, and redox-active micro/nanomaterials have been reviewed. Finally, the key challenges and critical perspectives of gut microbiota-based micro/nanomaterial treatment are also discussed.