Sleep disturbance is common in dialysis patients and is associated with the development of enhanced inflammatory responses. Cognitive-behavioral therapy is effective for sleep disturbance and reduces inflammation experienced by peritoneal dialysis patients; however, this has not been studied in hemodialysis patients. To determine whether alleviation of sleep disturbance in hemodialysis patients also leads to less inflammation, we conducted a randomized controlled interventional study of 72 sleep-disturbed hemodialysis patients. Within this patient cohort, 37 received tri-weekly cognitive-behavioral therapy lasting 6 weeks and the remaining 35, who received sleep hygiene education, served as controls. The adjusted post-trial primary outcome scores of the Pittsburgh Sleep Quality Index, the Fatigue Severity Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory were all significantly improved from baseline by therapy compared with the control group. The post-trial secondary outcomes of high-sensitive C-reactive protein, IL-18, and oxidized low-density lipoprotein levels significantly declined with cognitive-behavioral therapy in comparison with the control group. Thus, our results suggest that cognitive-behavioral therapy is effective for correcting disorganized sleep patterns, and for reducing inflammation and oxidative stress in hemodialysis patients.