Lead acetate poses numerous health risks and seriously harms living things' genetic makeup. Propolis and virgin olive oil (VOO) are both natural materials that contain anti-genotoxic chemicals as well as a variety of other advantageous properties for 16S rRNA sequencing. The current study was designated to determine the beneficial effects of virgin olive oil and propolis on lead acetate-induced genotoxicity in mice. Twenty-five male albino mice (Mus musculus) were divided into five groups of five mice each: the first group served as the control and received no treatment; the second, third, fourth, and fifth groups received 400 mg/kg B.W. of lead acetate orally, either dissolved in distilled water or dissolved in 8 mL/kg of VOO, or dissolved in 150 mg/kg of propolis, or 4 mg/kg B.W. of zinc chloride (ZnCl2), respectively. The second group exhibited a high genetic distance value, while the fifth group exhibited a low genetic distance value when compared with the control group. Propolis and virgin olive oil were found to be effective in lowering the genetic variation caused by lead acetate, with genetic distances of 0.0018 and 0.0026, respectively, according to the 16S rRNA sequence data. It concluded that propolis and virgin oil reduced lead acetate genotoxicity when compared with zinc chloride.