Background: Methotrexate is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases. Material and methods: 210 healthy adult male Swiss albino mice (Mus musculus), were allotted among three groups. The animal were given daily (0.065mg/ml) of methotrexate intraperitonealy followed by injection of Omega-3 plus at dose (8.58 mg/20g mice), Apple at dose (1.43 mg/20 g mice) and Psyllium at dose (18.2mg /20 g mice) for five days. Results: Various Structural and numerical chromosomal aberrations in bone marrow cells; mitotic activity and sperm head abnormality were recorded, quantitated, and statistically analyzed. Also DNA extraction and apoptosis detection in liver was done. The intensity of apoptotic bands located at 200 b p; 400b p ; 600 b p;800 b p and intact DNA measured by software Gel Pro program as maximum optical density values. Conclusion:, Methotrexate had adverse effect on chromosomal and sperm head structure, also it induce apoptosis, necrosis and decrease total DNA in mice liver.Omega-3 plus, Apple, and Psyllium attenuate the methotrexate-related toxic effects.