Ivermectin is a veterinary anthelminthic drug, highly effective against a number of arthropod and nematode infestations in vertebrates. The literature reported that ivermectin have mutagenic activities. The extensive use of ivermectin in food producing animals can cause potential hazard to humanity by causing gene mutation or chromosomal aberrations. Recently, there have been con- siderable efforts to search for naturally occurring substances that can inhibit, reverse, retard or pre- vent mutagenicity. A wide array of substances derived from edibles and medicinal plants reported to possess anticarcinogenic and antimutagenic activities. Therefore, the aim of this study was to evaluate the modulator role of each of garlic, L-carnitine and wheat germ oil (WGO) against geno- toxicity of ivermectin in buffalo lymphocyte cultures by using the cytokinesis block micronucleus assay and chromosomal aberrations test as cytogenetic end-points. Results showed that ivermectin induced dose dependent increase in the frequencies of the binucleated lymphocytes with micronuc- lei as well as the number of micronuclei in lymphocytes of river buffalo, while the number of bi- nucleated lymphocytes significantly decreased. In addition, ivermectin low dose caused non- significant increase in the frequency of total chromosomal aberrations in lymphocytes of river buf- falo as compared to control. Whereas, in medium and high doses the frequencies of aberrant cells increased at a significant level (P ≤ 0.001) than control. Meanwhile, the treatment with the three natural supplements (garlic, L-carnitine, wheat germ oil) in continuous with ivermectin significant- ly reduced the frequencies of binucleated lymphocytes with micronuclei, the number of micronuc- lei and the frequencies of total chromosomal aberrations induced by ivermectin tested doses, and increase the number of binucleated lymphocytes. In addition, the results indicated that there were non-significant differences between the modulator role of garlic, L-carnitine or wheat germ oil against the mutagenicity of ivermectin in blood lymphocytes. Finally, we can concluded that regu- lar consumption of natural antioxidants, antimutagenic compounds is inversely related to the risk of cancer, since the free radicals scavenger activities of antioxidants are very important due to the de- leterious role of free radicals in foods and in biological systems.