A rapid and cost-effective arm of the drug discovery and development process is finding new uses for existing drugs. Initially used as antibacterial agents, sulphonylureas were repurposed for the treatment of type 2 diabetes due to their hypoglycemic side effects. Their primary mechanism of action is mediated by binding to sulphonylurea receptors (SUR), which are atypical adenosine triphosphate binding cassette transporters in pancreatic beta cells. This interaction inhibits ATP-sensitive potassium channels to promote insulin release. Off-target actions of sulphonylureas identified in recent studies have demonstrated a range of anti-inflammatory properties mediated by modulation of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 inflammasomes. Inflammasomes are cytosolic protein complexes that assemble in response to infection or stress-associated stimuli, activating inflammatory responses, and are the primary source of pro-inflammatory cytokines. Sulphonylureas and their derivatives have been shown to inhibit various stages of inflammasome activation, leading to the reduction of pro-inflammatory mediators, including IL-1β and IL-18. Recent evidence demonstrates that these agents reduced inflammatory responses, disease severity, and progression in various preclinical autoimmune and inflammatory models. In this narrative review, we consider the complexity of autoimmune conditions and the limited treatment options, and highlight the potential value of repurposing sulphonylureas and their derivatives as adjunct therapeutics for autoimmune conditions.