Pyroptosis, a form of programmed cell death characterized by cell swelling and osmotic lysis, plays a complex role in both health and disease. This review provides an in-depth analysis of the mechanisms, regulation, and clinical perspectives of pyroptosis. Pyroptosis is initiated by the formation of inflammasomes, maturation of inflammatory caspases, and caspase-mediated cleavage of gasdermin. The function of pyroptosis is multifaceted, with both pro-inflammatory and anti-inflammatory roles. In diseases such as sepsis, uncontrolled pyroptosis can lead to severe outcomes, while in cancer, it can be exploited for therapeutic purposes. The review covers the historical development of pyroptosis research, including the discovery of key enzymes and pathways, and discusses the regulatory functions of pyroptosis in various diseases. It also explores promising therapeutic strategies, including small molecule inhibitors and traditional medicines, and highlights current challenges and future directions in clinical translation. The review emphasizes the importance of understanding pyroptosis for advancing disease therapy and developing novel treatments.Pyroptosis, a form of programmed cell death characterized by cell swelling and osmotic lysis, plays a complex role in both health and disease. This review provides an in-depth analysis of the mechanisms, regulation, and clinical perspectives of pyroptosis. Pyroptosis is initiated by the formation of inflammasomes, maturation of inflammatory caspases, and caspase-mediated cleavage of gasdermin. The function of pyroptosis is multifaceted, with both pro-inflammatory and anti-inflammatory roles. In diseases such as sepsis, uncontrolled pyroptosis can lead to severe outcomes, while in cancer, it can be exploited for therapeutic purposes. The review covers the historical development of pyroptosis research, including the discovery of key enzymes and pathways, and discusses the regulatory functions of pyroptosis in various diseases. It also explores promising therapeutic strategies, including small molecule inhibitors and traditional medicines, and highlights current challenges and future directions in clinical translation. The review emphasizes the importance of understanding pyroptosis for advancing disease therapy and developing novel treatments.