Purpose <p>Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Mitochondria are central to cardiac physiology, governing energy production, redox signaling, calcium homeostasis, and metabolic adaptation. Given their crucial role, mitochondrial dysfunction is increasingly recognized as a fundamental contributor to CVD progression. This review aims to provide an updated perspective on mitochondrial involvement in cardiovascular health and disease, emphasizing recent therapeutic advances and potential clinical applications.</p> Recent Findings <p>Mitochondrial dysfunction has been implicated in the pathogenesis of various CVDs, including heart failure, myocardial infarction, and ischemia–reperfusion (I/R) injury. Advances in mitochondrial-targeted drug development have identified novel therapeutic strategies, such as modulation of mitochondrial bioenergetics, dynamics, quality control, and signaling pathways. Additionally, emerging research has expanded our understanding of mitophagy, mitochondrial transfer therapies, and the role of mitochondrial-derived signals in cardiac pathophysiology.</p> Conclusion <p>Targeting mitochondrial pathways represents a promising therapeutic approach for managing CVDs. However, key challenges remain, including efficient drug delivery, off-target effects, and interpatient variability in response to mitochondrial interventions. This review not only explores these approches but also summarizes compounds currently in preclinical and clinical stages that directly affect mitochondrial function. Additionally, we discuss novel strategies, such as mitochondrial transplantation and advanced drug delivery systems, that may enhance therapeutic efficacy. A deeper understanding of mitochondrial biology and its systemic interactions will be essential for translating these innovations into effective clinical treatments for cardiovascular diseases.</p> Graphical Abstract <p>Treatment can impact on different mitochondrial functions in CVDs</p> <p></p>