Abstract: Pyroptosis, a programmed inflammatory cell death, is executed by gasdermin family members. In response to danger signals, gasdermin is subjected to protease-mediated cleavage and activation, releasing its N-terminal domain with membrane pore-forming activity.N-terminal gasdermin binds to cell membrane phospholipids, and oligomerizes and forms stable membrane pore structures, causing loss of membrane integrity and secretion of pro-inflammatory cytokines and alarmins. Gasdermin-mediated pyroptosis and inflammatory responses play key roles in multiple biological processes including infection, inflammatory diseases as well as cancers. This review introduces the activation and pore-forming mechanisms of gasdermin family members and their roles in the above-mentioned diseases, and also highlights the therapeutic potentials in the treatment of related diseases by targeting gasdermins.