Mitochondria, the essential organelles within cells, play a pivotal role in determining cellular fate. Their homeostasis is regulated by genes from both the nucleus and the mitochondria. Exercise stands out as an effective non-pharmacological approach to maintaining physical health. Research has demonstrated that exercise influences mitochondrial homeostasis through various epigenetic mechanisms, such as DNA methylation, non-coding RNAs, and histone post-translational modifications. These mechanisms contribute to the overall health of organisms and can positively impact the onset and progression of numerous diseases. This chapter explores the intricate ways in which epigenetic mechanisms regulate mitochondrial homeostasis and the influence of exercise on this process. Additionally, it summarizes the diverse roles of exercise in both physiological and pathological contexts, highlighting its effects on mitochondrial homeostasis and overall health through epigenetic pathways. The goal of this chapter is to provide theoretical insights and potential intervention targets related to the epigenetic mechanisms by which exercise enhances health, with a specific focus on the role of mitochondria.