Genotoxicity studies of plants with medicinal and nutritional properties are recommended by international regulatory agencies as part of the risk assessment. Due to their consumption as food, nutraceutical use and ethnopharmacological relevance, Campomanesia pubescens represents one of these plants to be studied. The aim of the present study was to evaluate the genotoxic, cytotoxic potential and clathogenic effects of the ethanolic extract obtained from the pulp of C. pubescens (EEFCP) fruits on rats submitted to experimental genotoxicity models and through the SMART test performed in Drosophila melanogaster. The comet assay and the micronucleus test were performed on peripheral and bone marrow blood, respectively, of Wistar rats orally treated with EEFCP at doses of 125, 250, 500 and 1000 mg per kg per bw for 28 days. In the SMART test, the standard cross between three mutant D. melanogaster strains was used. Larvae were treated with EEFCP at different concentrations and the wings of adult flies were evaluated for the presence/frequency of mutant spots and compared to the negative control group. Phytochemical analysis of EEFCP indicated high levels of flavonoids. The tests performed in rats showed that EEFCP did not present significant genotoxic or clastogenic effects. The biotransformation metabolites of EEFCP did not present genotoxic activity, as demonstrated by the SMART test. Together, all results indicate that, under the experimental conditions used, EEFCP did not reveal any preclinical genetic toxicity. Therefore, the safe consumption can be fomented increasing, consequently, the economic liquidity in the industrial market from the fruits of guavira.