BACKGROUND: This study aimed to investigate the effects of intradialytic concurrent (resistance-endurance) training combined with melatonin (MEL) supplementation on oxidative stress, inflammation, and cellular damage in hemodialysis (HD) patients. METHODS: Thirty-two HD patients were randomly assigned to three groups: Exercise (EX)-MEL, EX-Placebo (PLA), and Control (C)-PLA. Participants in the EX-MEL and EX-PLA groups underwent 12 weeks of concurrent training. Before nocturnal sleep, they ingested either 3 mg of MEL (EX-MEL) or a placebo (EX-PLA and C-PLA). Blood samples were collected at baseline and after 12 weeks of intervention to assess lipid peroxidation (malondialdehyde (MDA)), antioxidant biomarkers (ferric-reducing antioxidant power (FRAP), reduced glutathione (GSH), total thiol (THIOL)), total bilirubin (TBIL), uric acid (UA), biomarkers of muscle and liver damage (aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), creatine kinase (CK), lactate dehydrogenase (LDH), and Gamma-glutamyltransferase (Gamma-GT)), and inflammation (C-reactive protein (CRP)). RESULTS: EX-MEL demonstrated a decrease in MDA (p < 0.05) and CRP (p < 0.05), and an increase in FRAP (p < 0.05) pre- and post-training. Both EX-MEL and EX-PLA showed an increase in GSH (p < 0.001, and p < 0.05, respectively) and THIOL (p < 0.01, and p < 0.05, respectively) pre- and post-training. No significant changes were observed in TBIL, UA, ASAT, ALAT, CK, LDH, or Gamma-GT pre- and post-training across all groups. CONCLUSION: Concurrent training combined with MEL supplementation enhances oxidant-antioxidant balance and reduces inflammation in HD patients more effectively than intradialytic concurrent training alone.

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