Purpose: The purpose of this study is to evaluate the effectiveness of vitamin B12 treatment in subacute combined degeneration (SCD) caused by nitrous oxide (N2O) abuse. Methods: Relevant literature was accessed through PubMed, EMBASE, Scopus, and KoreaMed. All the literature that was relevant to human use of vitamin B12 treatment for SCD caused by N2O abuse was included. Case reports were excluded if the treatment regimens were not precisely described. The literature search was conducted by two investigators during September 2019 for the final publication period. The languages of the publications were restricted to English and Korean. Results: Twenty-three published articles that contained 24 cases were included. Sixteen cases among them were treated with intramuscular vitamin B12 of 1 mg/day and the rest received different doses or routes. Although most cases described significant clinical improvements, one case showed no beneficial effect due to the patient's noncooperation. Another case showed adverse events, including spinal myoclonus, following vitamin B12 therapy. Conclusion: Vitamin B12 has been broadly used for the treatment of SCD caused by N2O abuse. However, most of the relevant studies were case reports that reported various regimens of vitamin B12 administration. Further studies are needed to establish a standard regimen of vitamin B12 because the incidence of N2O abuse may increase in South Korea.