Objective:　Euodia　rutaecarpa,　(Wu　Zhu　Yu)　a　Chinese　medicine　clinically　used　to　treat　gastrointestinal　disorders,　has　been　widely　employed.　However,　Euodia　rutaecarpa　is　regarded　as　a　small　toxic　traditional　Chinese　medicine　in　the　Chinese　Pharmacopoeia　and　other　herbal　works.　Using　toxicity　predictions　combined　with　in　vitro　and　in　vivo　studies,　this　study　aimed　to　identify　the　toxic　components　and　toxic　target　organs　of　Euodia　rutaecarpa,　and　explore　its　toxic　mechanism　from　a　metabolic　perspective.　Methods:　The　toxic　target　organs　of　Euodia　rutaecarpa　were　identified　through　in　vitro　and　in　vivo　studies.　In　vitro　toxicity　screening　was　performed　by　alkaloid　enrichment　and　isolation.　The　potential　toxicity　of　compounds　was　predicted　by　Absorption,　Distribution,　Metabolism,　Excretion,　and　Toxicity　Predictor　(ADMET　Predictor)　based　on　Quantitative　Structure-Activity　Relationship　(QSAR)　construction.　In　addition,　the　study　integrated　the　serum　metabolomic　analysis　after　the　administration　of　potentially　toxic　components　to　clarify　the　effect　of　potentially　toxic　substances　on　metabolism　in　mice.　Results:　Comparing　the　acute　toxicity　in　mice　of　different　extraction　methods　and　before　and　after　processing,　it　was　evident　that　Euodia　rutaecarpa　alcoholic　extract　had　the　highest　toxicity,　and　the　target　organ　of　Euodia　rutaecarpa　toxicity　was　the　liver.　The　alkaloid　fraction　of　alcoholic　extract　of　Euodia　showed　strong　cytotoxicity.　The　potential　toxicity　of　Euodia　rutaecarpa　was　calculated　and　predicted　by　ADMET　Predictor,　and　alkaloids　are　suspected　to　be　responsible　for　the　toxicity　of　Euodia　rutaecarpa.　Evodiamine　significantly　reduced　the　number　of　cells　and　increased　the　mitochondrial　membrane　potential　in　vitro.　Different　metabolites　were　significantly　identified　by　serum　metabolomics,　of　which　bile　acid　metabolism　and　steroid　hormone　biosynthesis　are　the　key　pathways　of　hepatotoxicity.　Conclusions:　Clarify　the　scientific　significance　of　clinical　use　of　processed　products　by　comparing　the　acute　toxicity　of　different　extraction　methods　before　and　after　processing.　Combining　the　toxicity　prediction　based　on　QSAR　with　the　toxicity　screening　in　vitro　and　in　vivo,　the　potential　toxic　target　organs　and　toxic　components　of　Euodia　rutaecarpa　can　be　identified.　Through　metabolomics,　we　preliminarily　revealed　that　the　hepatotoxicity　of　Euodia　rutaecarpa　may　be　related　to　bile　acid　metabolism　and　steroid　hormone　biosynthesis.　This　study　lays　the　foundation　for　elucidating　the　mechanism　of　Euodia　rutaecarpa　and　evaluating　its　safety　and　quality.　　Copyright　©　2024　Tianjin　University　of　Traditional　Chinese　Medicine.