Chronic kidney disease (CKD) is a prevalent health issue that can have detrimental effects on the quality of life (QoL) of children. Nevertheless, with adequate management and support, many children with CKD can have satisfying lives. The study aimed to investigate the effect of muscle stretching and isometric exercises on QoL of children undergoing hemodialysis. Sixty-eight children aged 6-18years with kidney failure undergoing hemodialysis at Assiut University Children Hospital were included. They were randomly assigned to two groups. The study group received a 40-min exercise program three times per week for 2months, while the control group received routine hospital care. For outcome measures, two tools were used: a simple questionnaire sheet for personal and medical data and PedsQL™ scale. After 2months of exercise, it was shown that most children in the study group (66.7%) had good QoL, in contrast to only 3.3% in the control group, with a highly statistically significant variation between the two examined groups pertaining to the health-related QoL scale (P value = 0.001) after exercise. The intensity of care for children on hemodialysis has a distinguished impact upon their quality of life. The implementation of muscle stretching and isometric exercises during hemodialysis represents an important aspect of such care that may be associated with significant improvement in all domains of QoL. Children undergoing hemodialysis need well-organized programs that cover all physical and psychological aspects with smart time manipulation and increased attention from their staff.