OBJECTIVE: To systematically evaluate the efficacy and safety of glutathione (GSH) in preventing oxaliplatin-induced peripheral neurotoxicity (OIPN), and to provide evidence-based reference in the clinic. METHODS: Randomized controlled trials (RCTs) about therapeutic efficacy of GSH vs. placebo/no any measures (called placbo group) or other drug in preventing OIPN were retrieved from PubMed, EMBase, Cochrane library, CJFD, Wanfang database and VIP. Meta-analysis was performed with Rev Man 5.3 statistical software after data extraction and quality evaluation with Jadad scale. RESULTS: 18 RCTs were included, involving 1 200 patients. The results of Meta-analysis showed that: total incidence of oxaliplatin-induced chronic peripheral neurotoxicity (OICPN)[RR=0.71,95%CI(0.59,0.87),P<0.001] and the incidence of severe OICPN [RR=0.50,95%CI(0.42,0.60),P<0.001] in GSH group were significantly lower than placebo group, with statistical significance; there was statistical significance in the incidence of oxaliplatin-induced acute peripheral neurotoxicity (OIAPN)[RR=0.89,95%CI(0.72,1.09),P=0.25]. The incidence of severe OICPN in GSH group was significantly higher than mecobalamine group, with statistical significance [RR=2.06,95%CI(1.07,3.99),P=0.03]. There was no statistical significance in the incidence of OICPN[RR=1.38,95%CI(0.83,2.31),P=0.21] and severe OICPN [RR=1.91,95%CI(0.85, 4.30),P=0.12] between GSH group and Ca+Mg mixture group. CONCLUSIONS: GSH can effectively prevent the occurrence of OICPN, however, its therapeutic efficacy is equivalent to Ca+Mg mixture and inferior to mecobalamine in preventing severe OICPN.