PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 80% of patients undergoing cytotoxic chemotherapy. This painful condition significantly impairs quality of life and often necessitates dose reduction or discontinuation of chemotherapy, negatively impacting overall survival. Currently, duloxetine is the only pharmacological treatment recommended by the American Society of Clinical Oncology (ASCO). This systematic review aims to evaluate the efficacy of various pharmacological interventions in CIPN treatment, providing substantial evidence for clinical practice and future research. DESIGN: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess the effectiveness of pharmacological treatments for CIPN. METHODS: Only randomized controlled trials (RCTs) were included. Herbal and phytotherapeutic treatments were excluded. Two independent reviewers performed the study selection, with a third reviewer resolving disagreements. Risk of bias assessment was conducted using the COCHRANE's RoB 2 tool. RESULTS: Out of 860 screened articles, 17 RCTs met the inclusion criteria, encompassing 15 different pharmacological agents. Duloxetine, pregabalin, and amitriptyline were the most studied. Thirteen studies utilized a placebo as a control. Investigated medications exhibited varied outcomes, with some showing significant benefits in reducing neuropathic pain while others did not demonstrate statistically significant efficacy. CONCLUSION: Duloxetine is an effective and well-tolerated option, while pregabalin shows promising results but requires further investigation. Other agents, such as venlafaxine and tapentadol, lack strong supporting evidence. Treatments like acetyl-l-carnitine, monosialotetrahexo-sylganglioside 1, and tetrodoxine yield inconsistent results, highlighting the need for additional research. Larger RCTs are recommended for comprehensive evaluation. Nurses are essential in CIPN care by monitoring symptoms, educating patients, and collaborating with the team.