Background: Cerebellum, also known as the "small brain," is a highly stereotypical cortical structure located in the vertebrate hindbrain. Its primary function is to aid in motor control, but it also processes a wide range of sensory functions. Methotrexate (MTX) is widely used as a chemotherapy agent for treating many different kinds of cancer. Psoriasis, SLE, IBD, vasculitis, and a wide variety of other connective tissue illnesses can all benefit from it without any negative side effects. The neurological system is particularly vulnerable to methotrexate's adverse effects. Although neuronal symptom is also frequently observed. Since MTX-induced neurotoxicity has received less attention than its other side effects, its causes remain unknown. Objective: This review article aimed to assess the possible toxic effects of Di Ethyl phthalate (Methotrexate) on cerebellar cortex. Methods: Methotrexate, cerebellar cortex 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 study from January 2000 to May 2022 was included. Due to the lack of sources for translation, documents in languages other than English have been 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 Papers that did not fall under the purview of major scientific investigations, such as unpublished manuscripts, oral presentations, conference abstracts, and dissertations, were omitted.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: Purkinje cell shrinkage, karyolitic alterations in granule cells, and nuclear damage were observed as pathological changes at the cellular component of the cerebellar cortex after methotrexate exposure.