Post-cholecystectomy syndrome (PCS) is a persistent digestive disorder that persists after cholecystectomy surgery. Due to its complex etiology, difficult diagnosis, and diverse treatment options, PCS has long been a clinical challenge in the field of biliary surgery. This article reviews the multifactorial etiology of PCS, covering the latest progress in the pathogenesis of biliary factors, extrahepatic factors, and changes in the intestinal microbiota; analyzes the stratified application strategies of diagnostic techniques such as endoscopic ultrasound (EUS), SeHCAT scanning, and Oddi sphincter pressure measurement; summarizes various treatment strategies including dietary control, drug therapy, endoscopic intervention, and traditional Chinese medicine treatment; and assesses the application potential of the SECURE trial, the SUCCESS prediction model, and the PERFECT trial in preoperative patient screening, emphasizing the significance of precisely selecting surgical indications in reducing the risk of PCS occurrence.