The biological effects of molecular hydrogen are moving beyond the traditional explanatory framework of “selective antioxidation.” This article systematically integrates the basic, preclinical, and preliminary clinical evidence for hydrogen in metabolic diseases, neurodegenerative disorders, and cancer, centering on the two major themes of mitochondrial quality control and metabolic reprogramming. Current studies indicate that hydrogen can reshape redox homeostasis, coordinate mitochondrial biogenesis, dynamic balance, and mitophagy, and modulate key signaling axes such as AMPK/Sirtuins, PGC-1α, and PPARα, aimed at optimizing mitochondrial function, thereby influencing adaptive glucose and lipid metabolism as well as cellular bioenergetic homeostasis. Although its upstream initiating events and context dependency remain to be clarified, existing evidence supports the view that hydrogen is an important network regulator linking redox regulation, mitochondrial homeostasis, and metabolic adaptation.