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To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy.This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30).After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P0.01 or P0.05).WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).