Background Hemodialysis patients are highly vulnerable during the COVID-19 pandemic and face multiple challenges that affect their physical, psychological, social, and economic well-being. Objective This study aims to thoroughly investigate the experiences of end-stage renal disease patients undergoing hemodialysis during the COVID-19 pandemic. Methods A qualitative descriptive design was applied. Fifteen participants were recruited purposively from Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital. Data were collected through in-depth interviews and analyzed thematically, guided by Roy’s Adaptation Model to capture adaptive and maladaptive responses. Result There are three themes produced in this research: 1) various responses to the COVID-19 pandemic, 2) various impacts, and 3) coping mechanisms developed. Conclusion The findings underscore the importance of holistic nursing interventions, psychosocial support, and continuous professional development for dialysis nurses to strengthen patient resilience during current and future health crises.