<p>Erythrocytes, as the predominant cellular components within the bloodstream, are crucial for the maintenance of physiological health. Mitochondria, known as cellular powerhouses and metabolic regulators, play a critical role in the maturation of the erythroid lineage. The absence of mitochondria in red blood cells upon completing their maturation process is a defining characteristic of their development. Dysregulation of mitochondrial metabolism has been associated with the onset and progression of various diseases. Mitochondrial metabolic disorders, along with the involvement of mitochondria in the induction of oxidative stress and the activation of immune responses, significantly contribute to the pathogenesis of diverse hematologic disorders, particularly in sickle cell disease. This review offers a comprehensive overview of the role of mitochondria in disorders related to abnormal erythropoiesis, immune responses, and hemolysis, as well as evaluating potential therapeutic strategies that target mitochondria. Ultimately, we emphasize the necessity for future research to elucidate the involvement of mitochondria in red blood cell disorders, which may inform the development of novel diagnostic and therapeutic approaches.</p>