The NLRP3 inflammasome is a multi-protein complex that triggers inflammatory cell death and the release of pro-inflammatory cytokines IL-1β and IL-18. It plays a role in various diseases, including Alzheimer's, prion diseases, type 2 diabetes, and infectious diseases. Activation of the NLRP3 inflammasome is triggered by a variety of stimuli, including DAMPs and PAMPs, but the exact regulatory mechanisms remain unclear. Understanding these mechanisms is crucial for developing specific inhibitors to treat NLRP3-related diseases. Recent studies have identified several mechanisms of NLRP3 inflammasome activation, including ion fluxes, reactive oxygen species (ROS) production, and lysosomal destabilization. Post-translational modifications, such as phosphorylation and ubiquitination, also play a critical role in NLRP3 activation. Additionally, non-canonical and alternative inflammasome activation pathways have been identified. Several inhibitors, including MCC950, CY-09, OLT1177, Tranilast, and Oridonin, have been identified as potential treatments for NLRP3-related diseases. These inhibitors target NLRP3 directly, offering a promising approach for the treatment of NLRP3-mediated inflammatory conditions.The NLRP3 inflammasome is a multi-protein complex that triggers inflammatory cell death and the release of pro-inflammatory cytokines IL-1β and IL-18. It plays a role in various diseases, including Alzheimer's, prion diseases, type 2 diabetes, and infectious diseases. Activation of the NLRP3 inflammasome is triggered by a variety of stimuli, including DAMPs and PAMPs, but the exact regulatory mechanisms remain unclear. Understanding these mechanisms is crucial for developing specific inhibitors to treat NLRP3-related diseases. Recent studies have identified several mechanisms of NLRP3 inflammasome activation, including ion fluxes, reactive oxygen species (ROS) production, and lysosomal destabilization. Post-translational modifications, such as phosphorylation and ubiquitination, also play a critical role in NLRP3 activation. Additionally, non-canonical and alternative inflammasome activation pathways have been identified. Several inhibitors, including MCC950, CY-09, OLT1177, Tranilast, and Oridonin, have been identified as potential treatments for NLRP3-related diseases. These inhibitors target NLRP3 directly, offering a promising approach for the treatment of NLRP3-mediated inflammatory conditions.