ABSTRACT Chronic cholecystitis is a common disease that causes inflammation in the gallbladder and is usually associated with gallstones. Laparoscopic cholecystectomy has been widely used as a minimally invasive surgical technique to treat this condition. However, the clinical effect of laparoscopic cholecystectomy in the treatment of chronic cholecystitis with gallstones needs further investigation. This study aimed to investigate the clinical effect of laparoscopic cholecystectomy in treating chronic cholecystitis with gallstones. 90 patients with chronic cholecystitis and gallstones were randomly divided into control and research groups. The control group underwent traditional open cholecystectomy, while the research group received laparoscopic cholecystectomy. Perioperative indexes, oxidative stress indexes, serum inflammatory factors, liver function indexes and the incidence of complications were observed and compared. Results showed that laparoscopic cholecystectomy significantly reduced the operation time, blood loss, anal exhaust time, abdominal pain duration, and hospital stay compared to traditional open cholecystectomy (P < 0.05). Moreover, laparoscopic cholecystectomy significantly reduced the levels of oxidative stress indexes (GSH-Px), inflammatory factors (IL-6, TNF-α, and CRP), and liver function indexes (TBIL, AST, and ALT) compared to traditional open cholecystectomy. Moreover, the complication rate of the research group was significantly lower than that of the control group (P < 0.05). In conclusion, laparoscopic cholecystectomy for chronic cholecystitis with gallstones is a safe and effective procedure that reduces the perioperative stress response and promotes the rapid recovery of the postoperative body. The findings of this study provide a basis for the clinical promotion of laparoscopic cholecystectomy as the preferred surgical treatment for chronic cholecystitis with gallstones.