Concomitant administration of indomethacin with methotrexate is not recommended. Indomethacin is a non-steroidal anti-inflammatory drug that reduces prostaglandin synthesis by inhibiting the enzyme cyclooxygenase, thus providing anti-inflammatory, analgesic and antipyretic effects. Methotrexate, on the other hand, is a drug that inhibits DNA biosynthesis by inhibiting the enzyme dihydrofolate reductase, and the drug has toxicities such as myelosuppression, hepatic impairment, and teratogenicity. The combination of indomethacin and methotrexate enhances methotrexate toxicity. Indomethacin and methotrexate can cause drug interactions, so it is not recommended to use these two drugs at the same time, the patient’s drug treatment program should be formulated by the physician and follow the doctor’s instructions, unauthorized use of the drug may cause serious consequences. It is recommended that patients go to the relevant departments of regular hospitals for detailed counseling and take the medication as prescribed to avoid adverse effects.