Critical-sized　bone　defects　present　a　clinical　challenge　due　to　their　limited　self-repair　capacity.　Application　of　bone　tissue-engineering　scaffolds　often　overlooks　the　dynamic　modulation　of　the　microenvironment,　resulting　in　unsatisfactory　bone-regeneration　outcomes.　In　this　study,　a　bone　morphogenetic　protein-2-derived　peptide-loaded　honeycomb　manganese　dioxide　(BHM)　nanozyme　was　incorporated　into　a　composite　hydrogel　(BHM@CG)　composed　of　l-arginine-modified　methacrylated　carboxymethyl　chitosan　and　gallic　acid-grafted　methacrylated　gelatin.　This　hydrogel　demonstrated　a　cascade-regulated　enhancement　of　hemostasis,　antibacterial　activity,　anti-inflammatory　effects,　and　osteogenesis.　Initially,　the　BHM@CG　hydrogel　achieved　rapid　hemostasis　by　quickly　adhering　to　irregular　defects　upon　injury.　Subsequently,　it　displayed　robust　antibacterial　activity　through　synergistic　hydrogen　bonding,　hydrophobic　interactions,　and　cationic　interactions.　Meanwhile,　the　BHM　nanozyme　and　polyphenol　groups　from　gallic　acid　effectively　eliminated　reactive　oxygen　species,　enabling　long-term　inflammation　regulation.　Finally,　sustained　release　of　bioactive　components　promoted　cell　migration,　angiogenesis,　and　osteogenesis,　achieving　a　bone-formation　rate　of　nearly　40%　in　a　critical-sized　calvarial　defect　model　by　week　8.　More　interestingly,　the　hydrogel　also　demonstrated　efficient　antibacterial　and　bone-regeneration　capabilities　in　an　infected　critical-sized　calvarial　defect　model.　Overall,　this　hydrogel　dynamically　modulated　the　bone-defect　microenvironment　and　effectively　enhanced　bone　regeneration,　offering　a　promising　strategy　for　critical-sized　bone-defect　repair.　©　2025　American　Chemical　Society.