Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune and inflammatory reactions. IL-6 first binds to the IL-6 receptor (IL-6R), this complex then associates with gp130, inducing dimerization and the initiation of signaling through signal transducer and activator of transcription-3 (STAT3). Notably, the combination of soluble IL-6 receptor (sIL-6R) and IL-6 stimulates cells that only express gp130 and not IL-6R, a process known as trans-signaling. In contrast, soluble gpl30 (sgp130) serves as a natural inhibitor of trans-signaling. Accumulated evidence strongly supports the hypothesis that the development and perpetuation of inflammatory bowel disease (IBD) relies on IL-6-mediated STAT3 activation on mucosal T-cells. This review looks at therapeutic strategies targeting the IL-6/STAT3 pathway in patients with IBD, including strategies involving the anti-IL-6 receptor antibody and soluble gp130Fc.