The present study was carried out to evaluate the cytogenetic effects of the hexane extract of the plant Tribulus terrestris fruits. The cytogenetic evaluations involved mitotic index of bone marrow and spleen cells in albino male mice, micronucleus formation and sperm-head abnormalities. The micronucleus evaluations were further explored in blood lymphocyte cultures of healthy donors through an in vitro study. The search was carried out through three stages. In the first, the cytogenetic effects of three doses 5,10 and 20 mg/kg) of the plant extract were evaluated, while in the second stage, interactions Pre- and Post-treatments between the ideal dose 5 mg/kg of the plant extract and the drug Mitomycin-C (MMC). In stage three, the micronucleus formation was evaluated in the lymphocyte cultures of healthy individuals after treatment with three concentrations (5, 10 and 20 µg/ml) of the plant extract, in addition to interactions with the drug MMC which revealed significant mutagenic actions as judged by the investigated parameters. Reduced mitotic index, and increased frequencies of micronucleus formation (in vivo and in vitro) and sperm-head abnormalities were observed. The first stage revealed that the plant extract reduced the spontaneous formation of micronuclei and sperm-head abnormalities. The ideal dose 5 mg/kg of the plant extract was effective in modulating the mutagenic effects of the drug MMC. In this regard, the pre-treatment was more effective than post-treatment. The stage three showed that the plant extract was effective in reducing the spontaneous, as well as, MMC induced formation of micronuclei in lymphocyte cultures.