The present study was designed to shed light on the cytogenetic effects of tamoxifen in laboratory females' mice (in vivo), and in human blood lymphocytes (in vitro). It was also aimed to investigate the role of black seed oil and honey in reducing these effects in mice. The cytogenetic effects of the drug were investigated after one day, three and five days of treatment with two doses, low dose (0.4 mg/kg) and high dose (0.8 mg/kg). An interaction between black seed oil, honey and the drug (high dose) was carried out through two types of treatments (before and after drug treatment), to determine the activity of black seed oil and honey in preventing or reducing the drug effects. The following results were obtained:1- Tamoxifen revealed clear devastating effects, which were pronounced in reducing mitotic activity and increasing chromosomal aberrations and micronuclei in mouse bone marrow and human blood lymphocytes (in vitro). These effects were proportional with the number of doses, a phenomenon which suggested that the drug has an accumulated genotoxic effect. 2- Black seed oil and honey had no genotoxic effects on the bone marrow in albino mice. 3- Black seed oil and honey showed highly performance in protecting the bone marrow cells in mice against toxic tamoxifen effect by increasing the MI and decreasing the abnormal chromosomes and micronuclei when the treatment was before the drug, so black seed oil and honey were classified as desmutagen compounds in the first order. They had the ability to repair the tamoxifen destroyed cells, by increasing MI , repairing CA and decreasing MN in bone marrow cells in mice when treated after the drug , therefore , black seed oil and honey classified as bioantimutagens against tamoxifen in the second order.