Oxidative stress is a condition that might predispose the individuals to diseases including cancer. The 8-hydroxydeoxyguanosine (8-OHdG) is a marker that reflects oxidative DNA damage in the body. In this study, seven Saudi medicinal plants were investigated for their potential against oxidative DNA damage using the 8-OHdG assay in cultured human lymphocytes. Extracts at 10-100μg/mL from Nigella sativa black seeds, Olea chrysophylla (aerial parts) and Pulicaria crispa (aerial parts) significantly decreased levels of 8-OHdG (P<0.01), suggesting their usefulness as protective agents against oxidative DNA damage. The order of the antioxidative DNA damage effect of the extracts at 100μg/mL was Pulicaria crispa (36%)>>Olea chrysophylla (24%)>>Nigella sativa (18%). On the other hand, extracts of Bupleurum falcatum L at 100μg/mL induced significant increases in the 8-OHdG biomarker (P<0.01). Finally, Ficus palmate, Zygophyllum Simplex, Citrullus colocynthis did not modulate levels of 8-OHdG in cultured human lymphocytes at examined concentrations (10 and 100μg/mL, P>0.05). In conclusion, extracts from Nigella sativa, Olea chrysophylla and Pulicaria cripa medicinal plants can be used as useful agents to counteract oxidative DNA damage in cultured cells.