Purpose To investigate the role of oxidative stress and antioxidant system in the etiopathogenesis of pseudoexfoliation and progression of pseudoexfoliation syndrome to glaucoma. Material and method A total of 20 patients with pseudoexfoliation syndrome, 20 with pseudoexfoliation glaucoma, 20 with primary open-angle glaucoma, and 20 without pseudoexfoliation and glaucoma as a control group, who underwent cataract or glaucoma surgery between December 2020 and March 2021 in the Health Sciences University Beyoğlu Eye Training and Research Hospital, 80 patients were included in the study. Best corrected visual acuity (BCVA), intraocular pressure with applanation tonometry, detailed anterior and posterior segment examinations with biomicroscopy were performed in all patients included in the study. Approximately 0.1 cc of anterior chamber fluid was taken from all patients at the beginning of surgery. Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) levels were measured by keeping the samples taken in the deep freezer of the cornea bank at −80 degrees, transferring them with cold chain transport rules, and examining them with automatic measurement method in the laboratories of the Medical Biochemistry Department of the University of Health Sciences. Oxidative Stress Index (OSI) value was calculated to measure the degree of oxidative stress. Results TAS averages of the control and POAG groups were found to be statistically significantly higher than the PES and PEG groups (p = 0.0001, p = 0.0001). No significant difference was observed between the other groups (p > 0.05). The TOS averages of the control and POAG groups were found to be statistically significantly lower than the PES and PEG groups (p = 0.003, p = 0.0001; p = 0.01, p = 0.001), no statistically significant difference was observed between the other groups (p > 0.05). The OSI mean of the control and POAG groups was found to be statistically significantly lower than the PES and PEG groups (p = 0.001, p = 0.0001; p = 0.002, p = 0.0001), no statistically significant difference was observed between the other groups (p > 0.05). Conclusion Increased TOS and OSI and decreased TAS levels in the aqueous humour of patients with PES and PEG suggest that increased oxidative stress and decreased antioxidative defense system play a role in the etiopathogenesis of the disease.