The marine environment is a rich source of biological active compounds and the sponges can be considered the most productive one. This diversity gives rise to unique chemical compounds with potential pharmacological properties. Our study is focused on the genotoxic and antigenotoxic evaluation of two crude extracts obtained from the Brazilian endemic marine sponge Arenosclera brasiliensis. Salmonella typhimurium reverse mutation test with TA97, TA98, TA100 and TA102 strains were performed. For antimutagenic analysis, a pre-, co-, and post-treatment to evaluate, respectively, intracellular and extracellular reactions and possible modulation on DNA repair. Additionally, in order to verify the influence of the crude extracts on DNA damage induction, a plasmid-DNA treatment was assayed. No mutagenicity was observed in Salmonella reverse mutation test, neither DNA strand induced damage. Antimutagenic activity was observed in pre-, co-, and post-treatment. A significant antigenotoxic effect was observed in the crude extract, which suggests that A. brasiliensis extract has the potential to protect DNA from the action of 4NQO, 2-aminofluorene, sodium azide and mitomycin C.