The present work evaluated the protective effect of aqueous extract of Phyllanthus orbicularis against the mutagenicity of γ-radiation. The extract activity was determined in pre- and post-treatment procedures using Salmonella reversion assay. In either case, the plant extract protected bacterial cells against the mutations induced by γ-radiation, suggesting that it contains antimutagenic compounds which confer protection by at least two different mechanisms: i) as antioxidants targeting the oxidative mutagens induced by γ-radiation and ii) by modulation of the cellular repair enzymes acting on damaged DNA. The results are discussed in relation to the chemopreventive and radioprotective potential of P. orbicularis.