Background: Long-term treatment with low to moderate dosages of the antimetabolite and antifolate medication methotrexate (MTX) has been shown to be effective, safe, and well-tolerated for a wide range of autoimmune diseases. As a result, methotrexate may be used to treat vitiligo and other autoimmune disorders. The hepatotoxic and hematologic side effects of the drug's topical formulations, which were developed for the treatment of localized lesions, were deemed to be clinically insignificant. Objective: This review article aimed to assess the possible role oftopical methotrexate in the management of vitiligo. Methods: Methotrexate, and the vitiligo were all looked for in PubMed, Google scholar, and Science direct. References from relevant literature were also evaluated by the authors, but only the most recent or complete studies from January 2005 to May 2021 were included. Due to the lack of sources for translation, documents in languages other than English were ruled out. Papers that did not fall under the purview of major scientific investigations, such as unpublished manuscripts, oral presentations, conference abstracts, and dissertations, were omitted. Conclusion: Topical methotrexate use could be an effective and safe treatment modality of vitiligo.