Melatonin (MT) is a neurohormone released by the body. It has anti-infection, anti-inflammatory and antioxidant effects, and regulates the body’s normal sleep cycle. As an effective free radical scavenger and immune enhancer, it plays an important role in maintaining the normal physiological functions by acting on all systems and tissues of the body. Pyroptosis is a type of programmed cell death, in which the inflam-masomes and GSDMD (gasdermin D) family are the most important components. When the inflammasomes and the GSDMD protein are activated, membrane pores in the cell surface are generated, and a large amount of cellular fluid and intracellular substances are released, leading to a series of inflammatory cascade reactions, followed by secondary cell damage. Pyroptosis is closely related to the occurrence of many diseases. Mela-tonin, as an antioxidant and anti-inflammatory neurohormone, can cope with occurrence and development of myocardial damage, diabetes, central nervous system disease, obesity and degenerative disease by inhibiting pyroptosis. Herein, the effects of melatonin on pyroptosis in different diseases are reviewed.