BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS) and is the most common cause of neurologic disability in young adults (20-40 years old). About 2.5 million patients all over the world are suffering from MS. Common symptoms of the disease include sensory disorders, optic neuritis, and limb weakness. Following disease progression, other symptoms like fatigue, bladder disorders, and cognitive impairment also occur. Traditional Persian medicine (TPM) is an ancient medical system from 6000 years ago in Persia, where Iran was its most important state. TPM is a known humoral medical system. METHODS: In this review article, the traditional approach to MS and treatment methods in TPM literature are presented. TPM literature was written in the Persian and Arabic languages, the common scientific language of that era. Keywords defining MS were extracted from the well-known TPM books, such as Canon, Tebb-e-akbari, and Exire azam. The search covered known books from the 5 century to the 19 century. At the beginning, keywords such as Khaddar, Esterkha and Falej were considered. The search for herbal remedies was carried out according to the defined keywords in the main TPM manuscripts and especially in remedies (Mufradat) and treatment (Moalejat) TPM books, including Makhzan-ul-Adwiah, Al-abnieh Al-aghayegh Al-advie, Tuhfat-ul-Momineen, Gharabadin-e-Kabir, Gharabadine Shafaee, Tib-e-Akbari, and Exir-e-Azam. RESULTS: As the result of this review study, we managed to introduce categorized lists of herbal remedies and combinations used orally and in topical forms. Finally, comparative tables, including scientific names of plants, active components, and mechanisms showed the results of recent studies and phytotherapy research on TPM ancient remedies. CONCLUSION: Although we did not find MS in our search; however, there are some ailments with similar signs and symptoms in TPM literature. A list of various herbal medicaments has been introduced for these ailments, which should be evaluated critically during precise experimental and clinical studies.