Background: Inflammatory markers increase in end-stage renal disease (ESRD), especially in diabetic patients, and are positively correlated with cardiovascular mortality. Coenzyme Q10 (CoQ10), an agent with antioxidant properties, may be effective in reducing cardiovascular complications in hemodialysis patients. This study aimed to investigate the effects of CoQ10 supplementation on plasma C-reactive protein (CRP), homocysteine, and albumin in hemodialysis patients. Methods: Forty diabetic ESRD patients on hemodialysis for at least six months were evaluated in a double-blinded randomized clinical trial. The patients were randomly assigned to one of the two groups to receive either CoQ10 100 mg daily or placebo. In all patients, the serum levels of homocysteine, albumin, and CRP were measured before and after six months. Results: The mean age of the patients was 60.3 ± 9.1 years, and 57.5% of the participants were female. There was no statistical difference between the two groups at baseline. Furthermore, no significant difference was observed in serum albumin (P = 0.843), CRP (P = 0.214), and homocysteine (P = 0.21) at the end of the intervention between the groups. Conclusions: This study showed that in patients with ESRD, using CoQ10 supplementation has minimal beneficial effects on serum albumin, CRP, and homocysteine levels.