The　inadequate　vascularization　and　abnormal　immune　microenvironment　in　the　diabetic　bone　defect　region　present　a　significant　challenge　to　osteogenic　regulation.　Inspired　by　the　distinctive　characteristics　of　healing　staged　in　diabetic　bone　defects　and　the　structure-function　relationship　in　the　natural　periosteum,　we　fabricated　an　electrospun　bilayer　biomimetic　periosteum　(Bilayer@E)　to　promote　regeneration　of　diabetic　bone　defects.　Here,　the　inner　layer　of　biomimetic　periosteum　was　fabricated　using　coaxial　electrospinning　fibers,　with　a　shell　incorporating　zinc　oxide　nanoparticles　(ZnO　NPs)　and　a　core　containing　silicon　dioxide　nanoparticles　(SiO2　NPs)　mimicking　the　cambium　of　periosteum;　the　outer　layer　consisted　of　randomly　aligned　electrospun　fibers　loaded　with　deferoxamine　(DFO),　simulating　the　fibrous　layer　of　periosteum;　finally,　epigallocatechin-3-gallate　(EGCG)　was　coated　onto　the　bilayer　membrane　to　obtain　Bilayer@E.　The　presence　of　EGCG　on　the　Bilayer@E　surface　efficiently　triggers　a　phenotypic　transition　in　macrophages,　shifting　them　from　an　M1　proinflammatory　state　to　an　M2　anti-inflammatory　state.　Moreover,　the　sequential　release　of　ZnO　NPs,　DFO,　and　SiO2　NPs　exhibits　antimicrobial　characteristics　while　coordinating　angiogenesis　and　promoting　osteogenic　mineralization　in　cells.　Importantly,　the　biomimetic　periosteum　shows　strong　in　vivo　bone　tissue　and　periosteal　regeneration　properties　in　diabetic　rats.　The　integration　of　sequential　drug　release　and　immunomodulation,　tailored　to　meet　the　specific　healing　requirements　during　bone　regeneration,　offers　new　insights　for　advancing　the　application　of　biomaterials　in　this　field.　©　2025　American　Chemical　Society.