As　a　novel　antioxidant,　a　growing　body　of　studies　has　documented　the　diverse　biological　effects　of　molecular　hydrogen　(H-2)　in　a　wide　range　of　organisms,　spanning　animals,　plants,　and　microorganisms.　Although　several　possible　mechanisms　have　been　proposed,　they　cannot　fully　explain　the　extensive　biological　effects　of　H-2.　Mitochondria,　known　for　ATP　production,　also　play　crucial　roles　in　diverse　cellular　functions,　including　Ca2+　signaling,　regulation　of　reactive　oxygen　species　(ROS)　generation,　apoptosis,　proliferation,　and　lipid　transport,　while　their　dysfunction　is　implicated　in　a　broad　spectrum　of　diseases,　including　cardiovascular　disorders,　neurodegenerative　conditions,　metabolic　disorders,　and　cancer.　This　review　aims　to　1)　summarize　the　experimental　evidence　on　the　impact　of　H-2　on　mitochondrial　function;　2)　provide　an　overview　of　the　mitochondrial　pathways　underlying　the　biological　effects　of　H-2,　and　3)　discuss　H-2　metabolism　in　eukaryotic　organisms　and　its　relationship　with　mitochondria.　Moreover,　based　on　previous　findings,　this　review　proposes　that　H-2　may　regulate　mitochondrial　quality　control　through　diverse　pathways　in　response　to　varying　degrees　of　mitochondrial　damage.　By　combining　the　existing　research　evidence　with　an　evolutionary　perspective,　this　review　emphasizes　the　potential　hydrogenase　activity　in　mitochondria　of　higher　plants　and　animals.　Finally,　this　review　also　addresses　potential　issues　in　the　current　mechanistic　study　and　offers　insights　into　future　research　directions,　aiming　to　provide　a　reference　for　future　studies　on　the　mechanisms　underlying　the　action　of　H-2.