The most prevalent and costly diabetes-related consequence is diabetic neuropathy, with multiple therapies that failed to improve painful symptoms. An anti-oxidant and glutathione inducer, N-acetyl cysteine (NAC) has long been utilized as a mucolytic in individuals with specific lung problems and as an antidote for acetaminophen overdose, It also emerges as a promising treatment for treating diabetic peripheral neuropathy (DPN). This review aimed to assess the effect of acetyl cysteine on DPN. To identify relevant studies, Google Scholar, PubMed, Science direct, Egyptian Knowledge Bank (EKB), and clinical trial.gov were systematically searched. Pre-defined search terms were used; “NAC as an anti-oxidant", “NAC treatment", “acetyl cysteine treatment and DPN"," Diabetic Peripheral Neuropathy", “NAC in Neuropathic pain". Only English-based trials that are in full text were included.Seven studies were evaluated for NAC treatment effects in DPN. Randomized controlled trials and pre-clinical animal studies were the main interest of the review while pre-clinical studies including cell lines were excluded. In conclusion, most of the studies showed promising results in improving either the assessed scores or the biomarkers. Since most of the conducted studies were animal based studies, future clinical randomized controlled studies are essential to confirm the results.