Identification　of　natural　substances　with　antioxidant　properties　is　ongoing　research　for　addressing　issues　related　to　oxidative　stress　especially　attributed　to　environmental　effects.　Our　previous　study　demonstrated　that　Lateolabrax　japonicus　peptides　(LPH),　rich　in　Glu,　Gly,　and　hydrophobic　amino　acids,　exhibited　remarkable　antioxidant　activity　in　vitro,　with　though　its　action　mechanism　yet　to　be　revealed.　Therefore,　to　assess　the　in　vivo　antioxidative　properties　of　LPH,　we　employed　H2O2　to　generate　oxidative　stress　in　Drosophila　melanogaster　model.　Results　indicated　that　LPH　significantly　prolonged　the　lifespan　of　Drosophila　subjected　to　oxidative　stress　mostly　mediated　via　LPH’s　enhancement　of　the　antioxidant　defense　system　and　intestinal　functions.　Antioxidant　effects　were　manifested　by　a　decrease　in　malondialdehyde　(MDA)　levels,　elevated　superoxide　dismutase　(SOD),　catalase　(CAT),　and　glutathione　peroxidase　(GSH-Px)　activities,　decreased　levels　of　reactive　oxygen　species　(ROS)　in　intestinal　epithelial　cells,　and　the　preservation　of　intestinal　length.　LPH　effectively　controlled　the　excessive　proliferation　and　differentiation　of　oxidative　stress-induced　Drosophila　intestinal　stem　cells.　At　the　gene　level,　LPH　upregulated　the　expression　of　antioxidant-related　Nrf2　genes　while　concurrently　downregulated　mTOR　expression　level.　Furthermore,　high-throughput　16S　rDNA　sequencing　revealed　that　the　addition　of　LPH　significantly　influenced　the　diversity　and　abundance　of　the　intestinal　microbiota　in　H2O2-induced　Drosophila.　These　findings　provide　a　deeper　understanding　of　the　antioxidative　mechanism　of　LPH,　suggesting　its　potential　applications　in　food　industry　and　to　be　assessed　using　other　in　vivo　oxidative　stress　models.　©　2025　Beijing　Academy　of　Food　Sciences.