Gasdermin-D (GSDMD) belongs to the Gasdermin family (GSDM), which are pore-forming effector proteins that facilitate inflammatory cell death, also known as pyroptosis. This type of programmed cell death is dependent on inflammatory caspase activation, which cleaves gasdermin-D (GSDMD) to form membrane pores and initiates the release of pro-inflammatory cytokines. Pyroptosis plays an important role in achieving immune regulation and homeostasis within various organ systems. The role of GSDMD in pyroptosis has been extensively studied in recent years. In this review, we summarize the role of GSDMD in cellular and organ injury mediated by pyroptosis. We will also provide an outlook on GSDMD therapeutic targets in various organ systems.