Background:Despite regular treatment by hemodialysis, patients on hemodialysis are affected by uremic syndrome, which is marked by fatigue. Fatigue is supposed as the most common and the most severe symptom ever reported by patients with chronic kidney disease.Objectives:This controlled study aimed to evaluate the effect of intradialytic physical and mental exercises on fatigue in patients on hemodialysis.Patients and Methods:A total of 66 patients on long-term hemodialysis were selected via purposive sampling and were assigned to two groups, namely, control and experimental groups. The experimental group participated in a intradialytic training program twice a week for two months. The program was designed by a senior expert in physical education. Their fatigue was measured via a fatigue severity scale questionnaire before as well as one and two months after the intervention in both groups.Results:The mean of the fatigue score within the research units was 42.37. Overall, 42.2% and 56.1% of the participants experienced medium and severe fatigue, respectively. The scores of fatigue decreased significantly from the beginning through two months after intervention in the experiment group.Conclusions:With respect to the findings of the study, this method of treatment is recommended due to being cost efficient, easy, applicable, and flexible for alleviating the effect of fatigue on the personal, psychological, and social aspects of life quality in patients on hemodialysis.