Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as "molecular switch" in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn's disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment. Recently, several novel pathogenic components have been identified. In addition, potential therapies for IBD targeting Rho GTPases have emerged and proven to be clinically effective. This review mainly focuses on Rho GTPases and their possible mechanisms in IBD pathogenesis. The therapeutic possibility of Rho GTPases is also discussed.