Essential oil (EO) of Alpinia zerumbet leaves, at non-toxic concentrations (50-300μg/mL), did not induce genotoxicity in human leukocytes. However, at the highest concentration (500μg/mL) tested caused a reduction in cell proliferation and viability, and an increase in DNA damage. Moreover, in vivo experiments showed that EO (400mg/kg) did not exert mutagenicity on peripheral blood cells and bone marrow in mice. In DPPH test, EO showed scavenging effects against DPPH radicals, and other free radicals (determination of intracellular GSH and lipid peroxidation assays). Furthermore, EO was able to reduce the intracellular levels of ROS, and prevented leukocytes DNA against oxidative damage. The ability of EO to reduce H(2)O(2) toxicity was observed only when cells were treated with EO during and after exposure to H(2)O(2). With the co- and post-treatment procedures, EO decreased the frequency of apoptotic and micronucleated leukocytes as well DNA strand breaks. However, a synergistic effect was observed in cultures exposed to 500μg/mL EO. In conclusion, EO at concentrations up to 300μg/mL or doses up to 400mg/kg are not mutagenic in leukocytes and in mice, but do have antioxidative and protective effects against the cytotoxicity and clastogenesis induced by H(2)O(2).