Calendula officinalis L. (Asteraceae) is used in the traditional medicine for centuries to treat several diseases. The aim of the present study was to investigate in vivo the genotoxicity/mutagenicity and antigenotoxicity/antimutagenicity potential of the Calendula officinalis L. The CF-1 male mice were treated with ethanolic (250 or 500 mg/Kg) or aqueous (90 mg/Kg) extracts of C. officinalis for 2 weeks prior to treatment with saline or methyl methanesulfonate. No genotoxic or mutagenic effect was observed at the doses of ethanolic and aqueous extracts of C. officinalis in blood and bone marrow samples from animals after 2 weeks of treatment, analyzed by the Comet assay and Micronucleus test, respectively. In addition, ethanolic extracts in both doses (250 or 500 mg/Kg) and aqueous extracts (90 mg/Kg) of this plant showed an antigenotoxic effect by Comet assay, repairing the DNA damage caused by MMS. At the Micronucleus test only aqueous extract of C. officinalis revealed a protector effect to genetic material. These results suggest that all the extracts of C. officinalis contained protective substances that decreasing damage to genetic material. Despite this protective or antigenotoxic effect from this plant, it should be used with caution by the population.