Cardiovascular disease is the main cause of mortality in patients with chronic kidney disease stage 5 on dialysis (CKD-5D). High sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and neutrophil-lymphocyte ratio (NLR) are several inflammatory parameters associated with high cardiovascular events in CKD-5D. The main aim of this study was to evaluate the effect of reduced L-glutathione supplementation on serum hs-CRP, TNF-α, and NLR in patients with CKD-5D. This study is a quasi-experimental research with one group pretest-posttest design. Subjects included were patients with CKD-5D who routinely underwent hemodialysis therapy two times a week in Hasan Sadikin General Hospital. Serum hs-CRP, TNF-α, and NLR levels were obtained before and after the intervention of reduced L-glutathione supplementation dosing of one thousand milligrams a day for four weeks. Statistical analysis was then conducted using the Wilcoxon test. There were 26 hemodialysis patients included in the study, with a median age of 43 years and a male predominance. There was a significant decrease in serum TNF-α level after reduced L-glutathione supplementation for 4 weeks, 5.40 (-10.80-0.00) pg/mL, p = 0.002. However, there was no statistically significant decrease in either serum hs-CRP level, 0.40 (-0.70-0.80) mg/L (p = 0.656), or NLR with a difference of 0.55 (0.30-1.00) p = 0.055. Exogenous oral reduced glutathione supplementation for four weeks significantly reduced TNF-α level, but no significant decrease in hs-CRP level and NLR in patients with CKD-5D.