Background:　Hydrogen　peroxide　(H2O2),　a　novel　water　treatment　agent,　can　be　used　for　disinfection,　water　quality　adjustment,　and　disease　prevention,　while　excessive　H2O2　can　injure　farm　animals,　even　leading　to　death.　Hydrogen　peroxide　is　a　recommended　disinfectant　and　bactericide　for　treating　gill　diseases　and　vibriosis　in　the　greenfin　horse-faced　filefish　Thamnaconus　septentrionalis.　However,　its　cumulative　effect,　toxic　molecular　mechanism　and　relevant　signal　transduction/metabolic　networks　in　marine　fishes　are　largely　unknown.　Results:　We　employed　a　multi-omics　approach　to　investigate　the　detrimental　effects　of　50 mg/L　H2O2　exposure　(2 h/d)　on　filefish　for　2　d,　4　d,　and　6　d.　Transcriptome　sequencing　showed　that　differentially　expressed　genes　(DEGs)　were　mainly　classified　into　functions　such　as　signal　transduction,　nervous　system,　liver　and　bile　acid　metabolism,　energy　metabolism,　cell　adhesion　and　communication,　inflammation　and　immune　response.　Metabolomic　analysis　found　that　the　significantly　changed　metabolites　(SCMs)　were　involved　in　phenylalanine　metabolism,　inflammatory　mediator　regulation,　linoleic　acid　metabolism,　and　necroptosis.　The　main　SCMs　were　cholic　acid,　carnitine　C12:1,　dimethylmalonic　acid,　glutamic　acid,　L-lactic　acid,　shikimic　acid,　2-methylsuccinic　acid,　and　others.　Moreover,　H2O2-induced　oxidative　stress　also　disturbs　the　balance　of　the　gut　microbiota,　altering　the　microbial　composition　and　affecting　digestive　processes.　Conclusions:　Integrated　multiomics　analysis　revealed　that　H2O2-induced　detrimental　impacts　include　mucosal　damage,　inflammatory　and　immune　responses,　altered　energy　metabolism,　and　gut　microbiota　disorders.　These　findings　offer　novel　insights　into　the　harmful　effects　and　signal　transduction/metabolic　pathways　triggered　by　H2O2　exposure　in　marine　fishes.　©　The　Author(s)　2024.