The most popular form of treatment for end-stage renal illness is hemodialysis. Hemodialysis frequently causes muscle cramps and exhaustion, which negatively impact adolescents' activities, relationships, and treatment tolerance. This study aimed to evaluate the effect of nursing intervention using reflexology massage on muscle cramps and fatigue among adolescents undergoing hemodialysis. It employed a quasi-experimental design. The study was conducted at Mansoura University Children's Hospital and New General Mansoura Hospital on a purposive sample of 48 adolescents on maintenance hemodialysis. A structured questionnaire sheet, cramps questionnaire and visual analog scale and pediatric quality of life inventory-multidimensional fatigue scale were used to collect data. Significant differences were found in muscle cramps and fatigue levels between pretest and post-test (p=0.000 for each). The use of reflexology massage for adolescents undergoing hemodialysis had a positive effect on muscle cramps and fatigue levels. There is a need for courses that give nurses the opportunity to become certified in reflexology, and reflexology massage should be used as the evidence-base for nursing practice with children receiving hemodialysis.