Methotrexate, abbreviated MTX and formerly known as amethopterin, is an antineoplastic, antimetabolite and antifulate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Natural antioxidants such as fruits and vegetables, which provide protection against free radicals, can decrease the incidence and mortality rates of cancer and heart diseases, in addition to their other health benefits. Cornus mas fruits have anthocyanins, flavonoids, and plenty of oxalic acid content. It also contains antioxidant substances including butyrate hydroxyanisole and butylated hydroxytoluene, and has the potential to fight cancer. The present study indicated the hepatoprotective and nephroprotective effects of cornus mas fruit extract in methotrexate induced renal and liver injury in rat model.