Mitochondrial dysfunction is a key factor in many common diseases, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. Mitochondria, essential for cellular energy production and homeostasis, are involved in various functions such as lipid metabolism, calcium homeostasis, and apoptosis. Mitochondrial dysfunction can be primary, due to mutations in mitochondrial DNA, or secondary, caused by disease-related stress. The complexity of mitochondrial dysfunction makes it challenging to understand its role in disease, but it remains a promising therapeutic target. Recent advances in mitochondrial research have led to the development of various therapeutic strategies, including dietary supplements, pharmacological agents, and mitochondrial transplantation. These approaches aim to enhance mitochondrial function, reduce oxidative stress, and improve energy production. For example, nicotinamide riboside (NR) increases NAD+ biosynthesis, while MitoQ neutralizes reactive oxygen species (ROS) generated by mitochondria. Additionally, mitochondrial transplantation has shown promise in preclinical studies, with functional intact mitochondria being used to restore mitochondrial bioenergetics in recipient cells. Mitochondria also play a critical role in immune responses, as their components can act as extracellular signals that elicit immune reactions. Recent studies have shown that mitochondria can transfer between cells, a process that may contribute to tissue homeostasis and disease progression. However, clinical translation of these therapies remains limited due to challenges such as unstable mitochondrial vitality and inefficient cellular internalization. Mitochondrial dysfunction is closely linked to various diseases, including neurodegenerative disorders, metabolic diseases, and cancer. The mechanisms underlying mitochondrial dysfunction in these diseases involve impaired bioenergetics, increased oxidative stress, dysregulated calcium homeostasis, and altered mitochondrial dynamics. Understanding these mechanisms is crucial for developing effective therapies targeting mitochondrial dysfunction. The review highlights the importance of mitochondrial signaling in cell fate determination and the potential of mitochondrial-targeted therapies in treating common diseases.Mitochondrial dysfunction is a key factor in many common diseases, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. Mitochondria, essential for cellular energy production and homeostasis, are involved in various functions such as lipid metabolism, calcium homeostasis, and apoptosis. Mitochondrial dysfunction can be primary, due to mutations in mitochondrial DNA, or secondary, caused by disease-related stress. The complexity of mitochondrial dysfunction makes it challenging to understand its role in disease, but it remains a promising therapeutic target. Recent advances in mitochondrial research have led to the development of various therapeutic strategies, including dietary supplements, pharmacological agents, and mitochondrial transplantation. These approaches aim to enhance mitochondrial function, reduce oxidative stress, and improve energy production. For example, nicotinamide riboside (NR) increases NAD+ biosynthesis, while MitoQ neutralizes reactive oxygen species (ROS) generated by mitochondria. Additionally, mitochondrial transplantation has shown promise in preclinical studies, with functional intact mitochondria being used to restore mitochondrial bioenergetics in recipient cells. Mitochondria also play a critical role in immune responses, as their components can act as extracellular signals that elicit immune reactions. Recent studies have shown that mitochondria can transfer between cells, a process that may contribute to tissue homeostasis and disease progression. However, clinical translation of these therapies remains limited due to challenges such as unstable mitochondrial vitality and inefficient cellular internalization. Mitochondrial dysfunction is closely linked to various diseases, including neurodegenerative disorders, metabolic diseases, and cancer. The mechanisms underlying mitochondrial dysfunction in these diseases involve impaired bioenergetics, increased oxidative stress, dysregulated calcium homeostasis, and altered mitochondrial dynamics. Understanding these mechanisms is crucial for developing effective therapies targeting mitochondrial dysfunction. The review highlights the importance of mitochondrial signaling in cell fate determination and the potential of mitochondrial-targeted therapies in treating common diseases.