Traumatic　brain　injury　(TBI)　leads　to　high　rates　of　morbidity　and　mortality　worldwide　with　few　effective　treatments.　Excessive　oxidative　stress　and　local　inflammation　at　the　injury　site　are　considered　as　the　critical　factors　that　determine　the　therapeutic　outcome.　In　our　previous　study,　stem　cells　from　human　exfoliated　deciduous　teeth-derived　exosomes　(SHED-Exo)　promoted　functional　recovery　of　TBI　by　amelioration　of　neuro-inflammation.　However,　the　effect　was　restricted　due　to　unsustainable　exosome　release　and　existed　oxidative　stress　that　aggravate　secondary　insult　of　TBI.　To　obtain　a　long-time　anti-inflammatory　effect　of　SHED-Exo　and　attenuate　oxidative　stress　simultaneously,　we　designed　a　bioactive　antioxidant　poly　(citrate-gallic　acid)-based　hybrid　hydrogel　(FPGEGa)　that　encapsulate　SHED-Exo　for　treating　TBI.　The　thermosensitive,　injectable,　self-healing　and　antioxidant　FPGEGa　presented　ultralong　sustained　release　of　SHED-Exo　(above　21　days)　and　significantly　decreased　the　intracellular　ROS　production　of　microglia　in　the　central　nervous　system.　FPGEGa　carrying　SHED-Exo　(FPGEGa@SHED-Exo)　exhibited　better　anti-inflammatory　potential　on　microglia,　by　promoting　M2　(anti-inflammatory)　polarization　and　inhibiting　M1　(pro-inflammatory)　polarization.　FPGEGa@SHED-Exo　could　improve　the　neuro-regeneration　of　TBI　rats　by　rescuing　damaged　motor　functions　in　rats　as　well　as　regenerating　impaired　cortical　tissues.　The　present　work　suggested　that　SHED-Exo　engineered　bioactive　antioxidative　hydrogel　may　be　promising　in　achieving　satisfactory　functional　recovery　in　TBI　and　other　related　neurological　disorders.　©　2022　Elsevier　Ltd