Erva cidreira (Melissa officinalis) is a plant with sedative properties and in Brazil it has been used for insomnia and anxiety. It is also employed to stimulate liver functions and normalize menstruation and for intestinal constipation. The aim of this work was to evaluate the genotoxic and mutagenic effects of erva cidreira. Results indicate the presence of genotoxic activity in the lyophilized extract, with lysogenic induction increasing about 80-fold over the spontaneous background after treatment with lyophilized total aqueous extract. Beta-galactosidase levels raised 9-fold in indicator strains after treatment under the same conditions. A deeper look into the mechanism underlying the genotoxic action implicated reactive oxygen species generated by compounds retained in the ethyl-acetate, polar partition of the total aqueous extract. The spectrum of mutations revealed a great trend for base substitutions, mainly in guanines and adenines. The presence of phenolic compounds, especially caffeic acid derivatives, may be correlated to its genotoxic activity. We thus conclude that compounds present in current concentrations of erva cidreira extracts are genotoxic and mutagenic, and might have carcinogenic potential.