Methotrexate is an antifolate widely used in oncology and rheumatology that plays an important role in the treatment of acute lymphoblastic leukemia in children. One of its most common side effects is oral mucositis, which is a general term for ulceration and inflammation of the mucous membrane of the mouth. It can severely affect a patient's quality of life, causes poor nutrition, and may lead to discontinuation of the next course of chemotherapy. Oral mucositis typically develops a few days after chemotherapy infusion. Due to this risk, it appears reasonable to use preventive agents against oral mucositis before the inclusion of methotrexate in therapy. To date, clinical trials have examined the effectiveness of medications such as glutamine, palifermin, chlorhexidine, amifostine, cyclooxygenase-1 inhibitor, leucovorin or other methods including laser therapy and oral cryotherapy. There are also several methods used to control already established inflammation and reduce pain more effectively: laser therapy, platelet-rich plasma and platelet gel, taxifolin, film-forming and coating agents. A crucial role is played by supportive interventions involving analgesic treatment, including topical morphine and benzydamine and a modern approach to pain management -for example, the use of virtual reality.