Objective: The free radicals in the organism are important events in aortic valve sclerosis (AVS) because they cause conditions such as cell proliferation, growth arrest, and/or apoptosis and oxidation of low-density lipoprotein (LDL). This study was to evaluate DNA damage in patients with AVS and its relationship with thiol-disulfide homeostasis. Methods: Forty AVS subjects (30 female) were enrolled in this study and compared with control group. The diagnosis of AVS was made by comprehensive echocardiography. Biochemical parameters were measured in the sera of the control and AVS subjects. Results: In the AVS group, total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), disulfide, total thiol, natural thiol, disulfide/total thiol, disulfide/natural thiol, and oxidative 8-OH deoxyguanosine levels were significantly lower than those of the control group, whereas natural thiol/total thiol levels were significantly found to be higher. In addition, there was a statistically negative correlation between OSI and TAS in patient and control groups, and a positive correlation between OSI and TOS and natural and total thiol parameters. The results show DNA damage and impaired thiol-disulfide homeostasis. Conclusion: Our findings suggest that increased oxidant stress may signify an important point in the onset and progression of AVS. Therefore, adding antioxidants to treatment may shed light on new therapeutic targets for reinforcing the antioxidant system, slowing or even stopping aortic valve stenosis.