Human cathelicidin LL-37, the only member of the cathelicidin family of host defense peptides expressed in humans, plays a crucial role in host defense against pathogen invasion, as well as in regulating the functions of anti-inflammation, antitumorigenesis, and tissue repair. It is primarily produced by phagocytic leukocytes and epithelial cells, and mediates a wide range of biological responses. Emerging evidence from several studies indicates that LL-37 plays a prominent and complex role in inflammatory bowel disease (IBD). Although overexpression of LL-37 has been implicated in the inflamed and noninflamed colon mucosa in patients with ulcerative colitis, LL-37 expression was not changed in the inflamed or noninflamed colon or ileal mucosa in patients with Crohn's disease. Furthermore, studies in animal models and human patients further characterized the protective effect of cathelicidins both in ulcerative colitis and Crohn's disease. These data suggest the intricate functions of LL-37 in IBD. They will also create many strategies and opportunities for therapeutic intervention in IBD in the future. This review aims to elucidate the structure and bioactivity of LL-37 and also discuss the recent progress in understanding the relationship between LL-37 and IBD.