OBJECTIVE To investigate the distribution of prevalent traditional Chinese medical syndromes associated with bortezomib-related peripheral neuropathy(BiPN), the efficacy of Guicao Baidu(GCBD) decoction combined with a PD(bortezomib combined with dexamethasone)-based regimen in the treatment of BiPN patients, and the likely mechanism. METHODS A retrospective analysis of the clinical data of 17 myeloma patients with peripheral neuropathy associated with bortezomib was conducted. Peripheral neuropathy of varying degrees was observed in these individuals following a bortezomib-based regimen administered from January 2019 to December 2023. Symptom score scale was formulated for the objective BiPN syndrome differentiation. Peripheral neuropathy was evaluated using the National Cancer Institute's Common Toxicity Criteria for Adverse Events(NCI-CTCAE). GCBD decoction was administered orally. The effectiveness was assessed by looking at the visual analogue scale(VAS) score, neuroelectrophysiology, tumor treatment function evaluation/gynecological tumor group neurotoxicity subscale(FACT/GOG-Ntx) score, and NCI-CTCAE grade. The possible ingredients and targets of GCBD decoction in intervening BiPN were then predictd using mass spectrometry analysis and network pharmacology approaches. Molecular docking technology was utilized to confirm the binding activity between GCBD decoction's components and targets, while gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis were employed to investigate its mode of action. Furthermore, nerve growth factor(NGF)-induced PC12 cells were employed to generate a BiPN cell model. By assessing cell viability, reactive oxygen species(ROS) levels, neurite length, apoptosis levels, mitochondrial number, mitochondrial membrane potential, apoptotic protein expression, and mitochondrial translocation of BAX, the therapeutic mechanism of GCBD decoction was identified. RESULTS The syndrome differentiation types of BiPN patients were characterized mostly by qi and blood shortage, yang deficiency, cold coagulation, and blood stasis. GCBD decoction substantially reduced BiPN, peripheral neuropathy(PN) grade, FACT score, and VAS score(P<0.01 or P<0.05). Network pharmacology analysis obtained 3541 potential targets for GCBD decoction to interfere with BiPN, among which apoptotic proteins such as BCL2-Associated X (BAX), P53, B-cell lymphoma-2 (BCL-2), and Caspase-3 (CASP3) were the core targets. The GO and KEGG pathway enrichment indicated that one of the key pathways through which GCBD decoction intervened in BiPN was mitochondrial apoptosis. It was shown by molecular docking that several GCBD decoction monomers exhibited strong docking activity with the mitochondrial apoptotic proteins BAX, BCL-2, and CASP3. CONCLUSION This study preliminarily explors the TCM syndrome differentiation of BiPN patients, reveals the mechanism of GCBD decoction in inhibiting mitochondrial apoptosis and improving BiPN, and provids new ideas for reducing the toxic and side effects of chemotherapy in clinical practice.