•Inflammation consists of two successive steps; priming, a preparatory step and triggering, an activation step.•Key feature of triggering is the activation of inflammasomes, intracellular inflammatory protein complexes.•Caspase-11 non-canonical inflammasome is recently discovered and distinguished from the canonical inflammasomes.•Caspase-11 non-canonical inflammasome plays an aggravating role in IBD pathogenesis.•Caspase-11 non-canonical inflammasome also plays a protective role in IBD pathogenesis.•Selective regulation of caspase-11 non-canonical inflammasome may be therapeutic benefits for IBD and other inflammatory diseases. Inflammation is a two-step process comprising the first priming step that prepares inflammatory responses and the second triggering step that activates inflammatory responses. The key feature of the triggering step is the activation of inflammasomes and intracellular inflammatory protein complexes that provide molecular platforms to activate inflammatory signal transduction cascades. Although canonical inflammasomes have been well demonstrated to be actively involved in numerous human diseases, the roles of the recently identified non-canonical inflammasomes are largely unknown. However, recent studies have demonstrated the emerging roles of the caspase-11 non-canonical inflammasome in various human inflammatory diseases, ultimately providing strong evidence that the caspase-11 non-canonical inflammasome is a key player in the pathogenesis of various human diseases. Here, we comprehensively reviewed the regulatory roles of the caspase-11 non-canonical inflammasome in the pathogenesis of inflammatory bowel disease (IBD) and its underlying mechanisms. Overall, this review highlights the current understanding of the regulatory roles of the caspase-11 non-canonical inflammasome in IBD and may provide insight into new strategies for preventing and treating IBD and caspase-11 non-canonical inflammasome-driven diseases.