Real　time　detection　of　hydrogen　sulfide　(H2S)　in　deep　brain　regions　is　of　great　significance.　Photoelectrochemical　(PEC)　biosensors　hold　promise　for　real-time　monitoring　but　low　sensitivity　due　to　the　use　of　small　electrode　restrained　its　application.　In　this　study,　a　miniaturized　sensor　that　integrates　organic　photoelectrochemical　transistors　(OPECTs)　with　optical　fiber　(OF)　microelectrodes　was　designed　for　the　first　time,　which　can　amplify　the　small　PEC　signal　into　large　channel　current　change.　A　conductive　gold　layer　and　cuprous　oxide　nanoparticles　(Cu2O　NPs)　were　sequentially　deposited　onto　the　OF,　followed　by　a　Nafion　polymer　coating　to　enhance　anti-interference　capabilities.　Cu2O　reacts　with　H2S　to　generate　Cu2S.　The　resulting　Cu2O/Cu2S　heterojunction　induces　changes　in　the　PEC　signal　and　channel　current.　Compared　to　a　conventional　PEC　system,　the　OPECT　sensor　has　higher　sensitivity　and　lower　detection　limit,　enabling　monitoring　of　H2S　concentration　fluctuations　within　the　rat　brain,　which　demonstrates　the　approach’s　capability　for　highly　sensitive　in　vivo　biomarker　detection.　©　2025　American　Chemical　Society.