Cardiolipin，a pivotal lipid crucial for sustaining mitochondrial function，undergoes dynamic remodeling to accommodate fluctuating energy demands across both physiological and pathological contexts. Alterations in cardiolipin composition not only serve as indicators of mitochondrial functional states but also are intricately linked to the pathogenesis of numerous diseases，including cardiomyopathy，Parkinson’s disease，and age-related sarcopenia. Notably，exercise plays a crucial role in mitigating the detrimental health impacts of chronic diseases by modulating both the composition and levels of cardiolipin across various tissues. In this review， we provide a comprehensive synthesis of the latest advancements in understanding cardiolipin dynamics during exercise and pathological conditions，highlighting the synergistic interplay between mitochondrial biogenesis and cardiolipin biosynthesis in orchestrating mitochondrial function and accommodating shifts in energy metabolism.