Background:　A.　chinense　frequently　used　in　Miao　medicine　to　treat　rheumatic　diseases.　However,　as　a　famous　toxic　herb,　Alangium　chinense　and　its　representative　components　exhibit　ineluctable　neurotoxicity,　thus　creating　significant　challenges　for　clinical　application.　The　combined　application　with　compatible　herbs　in　Jin-Gu-Lian　formula　attenuates　such　neurotoxicity　according　to　the　compatible　principle　of　traditional　Chinese　medicines.Purpose:　We　aimed　to　investigate　the　detoxification　of　the　compatible　herbs　in　Jin-Gu-Lian　formula　on　A.　chinense-induced　neurotoxicity　and　investigate　its　mechanism.Methods:　Neurobehavioral　and　pathohistological　analysis　were　used　to　determine　the　neurotoxicity　in　rats　administered　with　A.　chinense　extract　(AC),　extract　of　compatible　herbs　in　Jin-Gu-Lian　formula　(CH)　and　combination　of　AC　with　CH　for　14　days.　The　mechanism　underlying　the　reduction　of　toxicity　by　combination　with　CH　was　assessed　by　enzyme-linked　immunosorbent　assays,　spectrophotometric　assays,　liquid　chromatography　tandem-mass　spectrometry　and　real-time　reverse　transcription-quantitative　polymerase　chain　reaction.Results:　Compatible　herbs　attenuated　the　AC-induced　neurotoxicity　as　evidenced　by　increased　locomotor　activity,　enhanced　grip　strength,　the　decreased　frequency　of　AC-induced　morphological　damage　in　neurons,　as　well　as　a　reduction　of　neuron-specific　enolase　(NSE)　and　neurofilament　light　chain　(NEFL)　levels.　The　combination　of　AC　and　CH　ameliorated　AC-induced　oxidative　damage　by　modulating　the　activities　of　superoxide　dismutase　(SOD)　and　glutathione　peroxidase　(GSH-Px),　and　total　antioxidant　capacity　(T-AOC).　AC　treatment　significantly　reduced　the　levels　of　monoamine　and　acetylcholine　neurotransmitters　in　the　brains　of　rats,　including　acetylcholine　(Ach),　dopamine　(DA),　3,4-dihydroxyphenylacetic　acid　(DOPAC),　homovanillic　acid　(HVA),　norepinephrine　(NE),　and　serotonin　(5-HT).　Combined　AC　and　CH　treatment　regulated　the　abnormal　concentrations　and　metabolisms　of　neurotransmitters.　Pharmacokinetic　studies　showed　that　the　co-administration　of　AC　and　CH　significantly　decreased　plasma　exposure　levels　of　two　main　components　of　AC,　as　evidenced　by　the　reduction　of　maximum　plasma　concentration　(C-max),　area　under　the　plasma　concentration-time　curve　(AUC)　compared　to　AC.　In　addition,　the　AC-induced　downregulation　in　mRNA　expression　of　cytochrome　P450　enzymes　was　significantly　reduced　in　response　to　combined　AC　and　CH　treatment.Conclusion:　Compatible　herbs　in　Jin-Gu-Lian　formula　alleviated　the　neurotoxicity　induced　by　A.　chinense　by　ameliorating　oxidative　damage,　preventing　abnormality　of　neurotransmitters　and　modulating　pharmacokinetics.