Oxaliplatin (OXA) is a widely used chemotherapeutic agent administered via intravenous infusion, primarily for the treatment of colorectal cancer. Despite its therapeutic efficacy, one of the most significant and common adverse effects associated with OXA is peripheral neuropathy, which can be dose-limiting and affect the patient’s quality of life.

Currently, there are no universally accepted preventive strategies for oxaliplatin-induced peripheral neuropathy (OIPN). However, the use of OXA in combination with various adjunctive agents has been explored to mitigate neuropathic effects, mainly through strategies that involve dose reduction or modulation without compromising the drug’s anticancer efficacy.

Several risk factors contribute to the onset and severity of OIPN. These include individual treatment regimens, cumulative dose, duration of therapy, and genetic polymorphisms that influence drug metabolism and nerve susceptibility. Notably, the long-term effects of OXA-induced neuropathy are most pronounced in the extremities, particularly the hands and feet, leading to sensory dysfunction and pain.

Although the exact pathophysiological mechanisms underlying OIPN remain unclear, a number of hypothesized biological pathways—such as oxidative stress, ion channel dysfunction, mitochondrial injury, and inflammatory responses—have been proposed in recent literature.

This review aims to examine and synthesize the latest advances in therapeutic approaches targeting OIPN, with the goal of supporting researchers and clinicians in developing mechanism-based interventions for the effective management of chemotherapy-induced peripheral neuropathy.