Organophosphorus insecticides (OPIs) are a common type of pesticides that have been mostly studied in adult animals, but their effects on early life stages are not well understood. In this study, we aimed to evaluate the genotoxic effect of profenofos (PFF), an OPI, on weanling male rats. The protective effect of Artichoke leaves extract (ALE), a natural antioxidant, against PFF-induced genotoxicity was investigated. ALE contains high amounts of phenolic and flavonoid compounds, such as gallic acid and chlorogenic acid, as determined by HPLC analysis. The extract also showed strong antioxidant activity in vitro, as measured by reducing power, DPPH●, and ABTS●+ assays. Weanling male rats was exposed to PFF at a dose of 14.32 mg/kg b.wt (1/25 LD50) with or without ALE at doses of 100 mg/kg and 200 mg/kg in drinking water for 28 days. We assessed the genotoxic and cytotoxic effects of PFF on the bone marrow cells using chromosomal aberrations, micronucleus, and mitotic index assays. The results showed that PFF significantly increased the frequency of chromosomal aberrations and micronucleus formation in the bone marrow cells and decreased the mitotic index in the exposed rats. The ALE reduced the genotoxic and cytotoxic effects of PFF on the bone marrow cells by decreasing the chromosomal aberrations and micronucleus formation and increasing the mitotic index. These findings suggest that PFF is a potential clastogenic/genotoxic agent, especially on early life stages that are more susceptible to its toxicity. The ALE can be used as a natural antioxidant and a protective agent against PFF-induced genotoxicity.