Cholera toxin B subunit (CTB) is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of DukoralŪ vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB`s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn`s disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models. This review summarizes the possible mechanisms behind CTB`s anti-inflammatory activity and discuss how the protein could impact mucosal inflammatory disease treatment.