Background: Mineral bone disorders pose significant challenges for patients with end-stage renal disease, contributing to morbidity and mortality. Nurse-led educational intervention program is effective strategy to empower patients in managing disease. Aim: The study aimed to evaluate the effectiveness of a nurse-led educational intervention program on symptoms, quality of life and progression of mineral bone disorders among patients with end-stage renal disease. Methods: Research design: A quasi-experimental non-randomized design. Sample and setting: A non-randomized sample of 120 patients with end-stage renal disease (control group = 60 patients, study group = 60 patients) was recruited and followed for 6 months in the hemodialysis unit of the internal medicine department at Assiut University Hospitals. Each patient in the study group received orientation and training from researchers on essential knowledge, and dietary recommendations to reduce phosphate intake, as well as exercises to improve bone health and provided with a handout booklet. Tools: The study utilized a patient assessment sheet, a numeric pain rating scale, and the EuroQol-5 dimension to measure outcomes. Results: The ages of patients in both groups ranged from 20 to 50 years. A nurse-led educational intervention program demonstrated a significant effect (p < 0.01) as regard all outcome measures; reducing symptoms, improving quality of life and limiting disease progression. Conclusion: A nurse-led educational intervention program notably reduced symptoms, enhanced quality of life, and slowed the progression of mineral bone disorders in patients with end-stage renal disease. Recommendation: Implementation of a nurse-led educational intervention program as a strategic approach to improve patient outcomes in managing mineral bone disorders associated with end-stage renal disease.