A　novel　photoelectrochemical　sensor,　employing　an　S-scheme　heterojunction　of　phthalocyanine　and　TiO2　nanoparticles,　has　been　developed　to　enable　highly　sensitive　determination　of　glutathione.　By　integrating　the　favorable　stability,　environmental　benignity,　and　electronic　properties　of　the　TiO2　matrix　with　the　unique　photoactivity　of　phthalocyanine　species,　the　designed　sensor　presents　a　substantial　linear　dynamic　range　and　a　low　detection　limit　for　the　quantification　of　glutathione.　The　sensitivity　is　attributed　to　efficient　charge　transfer　and　separation　across　the　staggered　heterojunction　energy　levels,　which　generates　measurable　photocurrent　signals.　Systematic　variation　of　phthalocyanine　content　reveals　an　optimal　composition　that　balances　light　harvesting　capacity　and　electron–hole　recombination　rates.　The　incorporation　of　phosphotungstic　acid　(PTA)　in　sample　preparation　effectively　minimizes　interference　from　compounds　like　L-cysteine　and　others.　Consequently,　this　leads　to　an　improvement　in　accuracy　through　the　reduction　of　impurity　levels.　Appreciable　photocurrent　enhancements　are　observed　upon　introduction　of　both　oxidized　and　reduced　glutathione　at　the　optimized　composite　photoanode.　Coupled　with　advantageous　features　of　photoelectrochemical　transduction　such　as　simplicity,　cost-effectiveness,　and　resistance　to　fouling,　this　sensor　holds　great　promise　for　practical　applications　in　complex　biological　media.　Graphical　Abstract:　(Figure　presented.)　©　The　Author(s),　under　exclusive　licence　to　Springer-Verlag　GmbH　Austria,　part　of　Springer　Nature　2024.