Efficient　management　of　difficult-to-heal　diabetic　wounds　remains　a　clinical　challenge　owing　to　bacterial　infections,　as　well　as　oxidative　and　hyperglycemic　complex　pathology.　Therefore,　developing　intelligent　strategies　for　diabetic　wound　healing　is　urgently　needed.　Herein,　an　ultrasound　(US)-responsive　microneedle　(MN)　patch　(MN@GOX@TiO2-X@CO)　capable　of　controlled　delivery　of　carbon　monoxide　(CO)　gas　within　the　skin　for　effective　treatment　of　diabetic　infected　wounds　is　developed.　Benefiting　from　the　specific　form　of　microneedle　(MN)　patch,　sonosensitizer　(TiO2-X),　•OH-responsive　CO　prodrug　(MPA-CO),　and　glucose　oxidase　(GOX)　can　be　loaded　together　and　effectively　delivered　to　infectious　wounds.　With　the　semi-fluidic　hyaluronic　acid　(HA)　coating　under　the　physiological　condition,　CO　could　be　released　efficiently　in　situ　and　directly　acted　on　infected　wound　tissue　upon　US　triggering.　Both　in　vitro　and　in　vivo　results　showed　that　US-triggered　CO　release　from　MN@GOX@TiO2-X@CO　not　only　effectively　inhibited　the　S.　aureus　and　MRSA　infection　but　also　promoted　fibroblasts　proliferation　and　migration　under　hyperglycemic　physiology,　thereby　accelerating　diabetic　wound　healing.　Collectively,　the　approach　effectively　addresses　the　impaired　skin　regeneration　function　in　diabetic　wounds　and　offers　a　promising　therapeutic　strategy　for　the　efficient　healing　of　infected　diabetic　wounds.　©　2024　Wiley-VCH　GmbH.