Objective: To investigate the correlation between depression severity and oxidative stress in patients undergoing hemodialysis (HD) using thiol disulfide homeostasis (TDH). Study Design: Descriptive, analytical study. Place and Duration of Study: Konya Health Application and Research Center, Konya, Turkey from September 2019 to March 2020. Methodology: A total of 67 patients including 35 males (52.2%) and 32 females (47.8%), receiving HD treatment, were included in the study. The Hamilton depression rating scale (HAM-D) was applied to the participants. Thiol disulfide homeostasis (total thiol (TT), native thiol (NT), disulfide, disulfide/NT ratio, disulfide/TT ratio, and NT/TT ratio) parameters, albumin, and ischemia modified albumin (IMA) levels were determined. The study groups were investigated by dividing them into groups according to their gender and HAM-D score. Results: According to HAM-D score, there were 32 (47.8%) patients with depression symptom (DS, HAM-D score of ≥8) and 35 (52.2%) patients without DS (HAM-D score: 0-7). Modified Charlson comorbidity index (MCCI), disulfide, disulfide/NT%, and disulfide/TT% levels were statistically and significantly higher and NT/TT% was statistically and significantly lower in DS group than the values of the groups without DS (p = 0.003, p =0.043, p = 0.017, p=0.017 and p = 0.017, respectively). HAM-D score and MCCI were statistically and significantly higher in females than males (p <0.001, p = 0.001, respectively). While, 21 patients (65.6%) had DS in women; according to HAM-D score, this rate was found to be statistically higher than men (11 patients, 31.4%, p = 0.005). Conclusion: Almost half of HD patients had at least moderate depression symptoms. In the group of HD patients with DS, TDH shifted in the oxidative direction. This may contribute to the future studies in enlightening depression etiology in HD patients.