© 2022 College of Physicians and Surgeons Pakistan. All rights reserved.Objective: To determine the changes in thiol/disulphide homeostasis in patients determined with asymptomatic cholelithiasis and to investigate any potential correlation between these thiol-disulphide parameters and HDL cholesterol. Study Design: A descriptive, comparative study. Place and Duration of Study: Ankara City Hospital between 15 September and 31 December 2019. Methodology: This study included 42 patients aged 18-70 years, who presented at the Gastroenterology Clinic and were diagnosed with cholelithiasis on ultrasound examination. A control group was formed of 51 healthy volunteers aged 18-70 years. Thiol/disulphide homeostasis and HDL cholesterol was noted and compared between the groups. Results: The mean age was 44.16 ± 13.35 years in cholelithiasis patient group and 31.88±13.27 years in the control group. The triglyceride, VLDL, total cholesterol/HDL, and non-HDL levels were significantly higher and HDL level was significantly low in the patient group (both p <0.05). Regarding thiol-disulphide balance, native thiol, total thiol, and albumin values were found to be statistically significantly low in the patient group (p <0.05), and the IMA, index-1, index-2, and index-3 values were significantly high (p <0.05). Conclusion: The oxidant/antioxidant balance shifted towards oxidation in patients with asymptomatic gallstones. The non-HDL value was increased. There was a positive correlation between the thiol-disulphide parameters and the non-HDL value. The increasing non-HDL amount could be effective in the pathogenesis of gallstone disease by disrupting the oxidative balance.