Organismal metabolism commences with dietary nutrient intake, followed by digestion and absorption in the gastrointestinal tract. This process involves intricate crosstalk between host physiology and gut microbiota, with downstream effects on hepatic metabolism, pancreatic endocrine function, and skeletal muscle bioenergetics. Exercise imposes systemic metabolic stress, triggering adaptive responses in multiple tissues to meet increased energy demands of contracting muscles. Recent studies have identified exercise-derived metabolites as critical signaling molecules that modulate epigenetic machinery, including histone-modifying enzymes and DNA methyltransferases. Consequently, the complex regulatory network of metabolic epigenetic reprogramming induced by exercise has received extensive attention.