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Peripheral neuropathy (PN) is one of the most common disorders characterized by the dysfunction or degeneration of peripheral nerves and has many different causes. PN often causes weakness, numbness, and pain, usually in the hands and feet, which can cause physical disability and a reduced quality of life. The purpose of this study was to conduct a review of the potential neuroprotective properties of progesterone against PN. A comprehensive systematic search was performed in many electronic databases (Scopus, PubMed, and Web of Science) until January 2024, following the PRISMA principles. A total of 72 studies underwent screening based on predetermined criteria for inclusion and exclusion. Ultimately, the present systematic review comprised 18 publications that satisfied the inclusion criteria. The data indicate that progesterone medication decreases PN by inhibiting the biochemical and morphological abnormalities caused by aging, diabetes, chemotherapy, and physical injury to peripheral nerves. However, as compared to the PN groups alone, progesterone treatment demonstrated tendencies towards being anti-oxidant, anti-inflammatory, anti-nociceptive, and neurodegenerative. Other studies have shown that PN also induces substantial biochemical changes in neuronal cells and tissues. Furthermore, we observed histological changes in the peripheral nerve tissue after PN. Overall, progesterone administration reversed these biochemical and histological alterations induced by PN in the vast majority of instances. Notably, the PN is ameliorated through progesterone administration. Progesterone achieves these neuroprotective effects through the inhibition of multiple mechanisms that are implicated in PN.