Purpose Peripheral neuropathy is a complication of taxane that in severe cases can limit the optimal treatment. The aim of this study was to evaluate the efficacy of memantine in prevention of docetaxel induced peripheral neuropathy in patients with breast cancer. Methods In this randomized clinical trial, 40 women between the ages of 18 and 64 years with non-metastatic breast cancer (stages I to III) were included (registry number: IRCT20160310026998N9 and registry date: 26 March 2019). All patients were treated with the AC-T regimen (with docetaxel). Patients in intervention group received memantine at a dose of 20 mg for 8 weeks at the beginning of the first cycle of docetaxel. Patients in control group did not take any medication for neuropathy prevention. To assess the neuropathy, DN4 and CTCAE questionnaires were used at baseline, one months, three months and six months after the intervention. Results The DN4 questionnaire score was remarkably less in memantine group in follow up one (p-value: 0.033) and three (p < 00.1). The CTCAE follow up score did not change during study. The Neuropathy duration and Neuropathy onset, were shown significant difference between the intervention and control groups, p = 0.050 and p = 0.001, respectively. From 40 patients, 8 (40%) in memantine group and 2 (10%) in control group, did not experience any kind of neuropathy. Conclusion Data showed that prophylactic administration of memantine 20 mg/day has been effective in prevention of severity and incidence of docetaxel induced neuropathy in patients with breast cancer.