Protein　disulfide　isomerase　(PDI)　can　catalyze　the　formation,　breakage　and　rearrangement　of　disulfide　bonds,　and　promote　protein　folding,　which　is　essential　to　stabilize　the　three-dimensional　structure　of　proteins.　The　dysregulation　of　PDI　expression　or　enzyme　activity　is　closely　related　to　a　series　of　diseases,　such　as　cancer,　neurodegenerative　diseases,　and　thrombosis.　In　this　review,　we　summarized　the　structure　of　PDI,　its　relationship　with　diseases　and　the　research　progress　of　its　inhibitors.　We　also　pointed　out　the　current　problems　and　the　development　direction　of　PDI　inhibitors,　which　will　provide　references　for　its　further　research.