Pyroptosis is a unique form of programmed cell death characterized by intense inflammation. It involves the activation of Gasdermin proteins, which form membrane pores, leading to rapid cell rupture and the release of inflammatory molecules. Unlike other types of cell death, pyroptosis has distinct activation mechanisms and plays a complex role in chronic intestinal diseases, including inflammatory bowel disease, intestinal fibrosis, chronic infectious enteritis, and colorectal cancer. This review comprehensively examines how pyroptosis influences disease development and progression while exploring the therapeutic potential of targeting pyroptosis-related pathways. Moreover, the complex interplay between gut microbiota and pyroptosis is summarized, highlighting its critical role in the pathogenesis of chronic intestinal disorders. A deeper understanding of pyroptosis-related mechanisms in these diseases may provide valuable insights for future research and contribute to the development of innovative therapeutic strategies in gastroenterology.