<p>Pyroptosis, a form of programmed cell death characterized by inflammation, plays a significant role in the pathogenesis of lung injury. This review explores the intricate relationship between pyroptosis and lung injury, emphasizing the critical role of pyroptosis in exacerbating inflammatory responses and tissue damage. Furthermore, the study delves into the complex interactions between pyroptosis and other cell death pathways. A comprehensive review of current pharmaceutical interventions targeting pyroptosis provides insights into potential therapeutic strategies. Multiple natural compounds confer lung protection by targeting specific molecular pathways. Compounds such as baicalin, baicalein, scutellarin, arteannuin B, resveratrol, silymarin, quercetin, and sinensetin inhibit pyroptosis through the modulation of NLRP3, caspase-1, or GSDMD pathways. Additionally, several synthetic small molecule drugs, including MCC950, disulfiram, VX765, and dimethyl fumarate, effectively intervene by binding to essential pyroptosis effector proteins. The use of NLCs enhances the in vivo bioavailability of these poorly soluble compounds and improves their targeted enrichment within damaged lung tissue. Furthermore, mesenchymal stem cells and their derived exosomes suppress pyroptosis via microRNA-mediated regulation of NLRP3, caspase-1, and GSDMD. Although existing preclinical data substantiate the anti-injury efficacy of these agents, many candidate drugs encounter significant translational challenges, including low oral bioavailability, unstable metabolic profiles, and inadequate in vivo targeting specificity. This review aims to enhance our understanding of lung injury and pyroptosis while summarizing new therapeutic approaches and drugs, which hold significant implications for addressing the occurrence and progression of lung injury.</p>