The　white　rot　fungus　Cerrena　unicolor　87613　has　been　previously　shown　to　be　a　promising　resource　in　laccase　production,　an　enzyme　with　significant　biotechnological　applications.　Conventional　methods　face　technical　challenges　in　improving　laccase　activity.　Attempts　are　still　being　made　to　develop　novel　approaches　for　further　enhancing　laccase　activity.　This　study　aimed　to　understand　the　regulation　of　laccase　activity　in　C.　unicolor　87613　for　a　better　exploration　of　the　novel　approach.　Transcriptomic　and　metabolomic　analyses　were　performed　to　identify　key　genes　and　metabolites　involved　in　extracellular　laccase　activity.　The　findings　indicated　a　strong　correlation　between　the　glutathione　metabolism　pathway　and　laccase　activity.　Subsequently,　experimental　verifications　were　conducted　by　manipulating　the　pathway　using　chemical　approaches.　The　additive　reduced　glutathione　(GSH)　dose-dependently　repressed　laccase　activity,　while　the　GSH　inhibitors　(APR-246)　and　reactive　oxygen　species　(ROS)　inducer　(H2O2)　enhanced　laccase　activity.　Changes　in　GSH　levels　could　determine　the　intracellular　redox　homeostasis　in　interaction　with　ROS　and　partially　affect　the　expression　level　of　laccase　genes　in　C.　unicolor　87613　in　turn.　In　addition,　GSH　synthetase　was　found　to　mediate　GSH　abundance　in　a　feedback　loop.　This　study　suggests　that　laccase　activity　is　negatively　influenced　by　GSH　metabolism　and　provides　a　theoretical　basis　for　a　novel　strategy　to　enhance　laccase　activity　by　reprogramming　glutathione　metabolism　at　a　specific　cultivation　stage.