BACKGROUND: In the presence of advanced age and comorbidities, patients with gallstones may face gangrenous and perforated cholecystitis during their follow-up. In the literature, dynamic thiol/disulfide homeostasis has been shown to play an important role in detoxification, antioxidant protection, regulation of enzymatic reactions, and apoptosis and cellular signaling mechanisms. In this study, we aimed to evaluate the efficacy of IMA and thiol/disulfide homeostasis in the preoperative diagnosis of patients with cholelithiasis, acute/chronic cholecystitis, and perforated gallbladder. METHODS: Sixty-six patients that presented to the General Surgery Clinic of Ankara City Hospital for a cholecystectomy operation between February 2019 and May 2020 were included in this study. The patients were divided into three groups depending on the condition for which they were scheduled for surgery: cholelithiasis, cholecystitis, and perforated gallbladder. The demographic data, history of cholecystitis, chronic disease, white blood cell (WBC), amylase, lipase and liver function tests (AST and ALT) were recorded before the operation. Gallbladder appearance was evaluated using hepatobiliary ultrasonography. The duration of surgery, pericholecystic adhesions, hospital stay, body mass index (BMI), postoperative complications, and pathology results of specimens were recorded. In addition, thiol/disulfide and IMA values were analyzed in the blood samples taken from the patients preoperatively. RESULTS: The mean native thiol and total thiol values of the patients with an adhesion score of 0 were significantly higher than those with an adhesion score value of 1, 2 or 3. In addition, the disulfide, disulfide/native thiol, native thiol/total thiol and IMA values of the cases with an adhesion score of 2 or 3 were significantly higher than those with an adhesion score of 0. The native thiol and total thiol averages of the patients with normal cholecystectomy were higher than the others. The disulfide, native thiol/total thiol and IMA averages of those who underwent cholecystectomy due to a perforated gallbladder were also higher than the other groups. The mean preoperative WBC of the patients who underwent cholecystectomy due to a perforated gallbladder was also significantly higher than the other groups. Lastly, the native thiol and total thiol values had a statistically significant negative correlation with age, operation time, and hospital stay, and a statistically significant positive relationship with BMI. CONCLUSION: We consider that in the preoperative diagnosis of the perforated gallbladder, the evaluation of thiol/disulfide hemostasis and IMA parameters can be used as an effective and reliable method to predict intraoperative difficulties.