Abstract: The pregnane X receptor (PXR) is a crucial member of the nuclear receptor superfamily and plays a pivotal role in regulating various biological processes. In recent years, significant progress has been made in the development of PXR antagonists and PXR-targeting proteolysis-targeting chimera (PROTAC). This review systematically summarizes recent advances in the study of PXR antagonists and PXR PROTAC drugs, with the aim of providing valuable insights and references for novel drug development and the exploration of new therapeutic targets in related fields.