This study was conducted to evaluate the antimicrobial activity and the genotoxic effects of ethanolic and aqueous extracts of aerial parts of Ephedra foeminea (E. foeminea) plant on Escherichia coli (E. coli ATCC 25922). Antimicrobial activity was investigated using microbroth dilution method, while the genotoxic effect was determined using enterobacterial repetitive intergenic consensus (ERIC)-PCR. MIC value of both ethanolic and aqueous extracts of E. foeminea plant was found to be 50 mg/ml. Genotoxic effects of both extracts, showed an alteration in (ERIC)-PCR profiles of E. coli strain treated with extracts compared to untreated control. These alterations included a decreased intensity or absence of some amplified fragments. Such findings strongly indicate the genotoxic effects of both ethanolic and aqueous extracts from E. foeminea plant on E. coli. The findings draw attention to the unsafe, use of E. foeminea plant in folkloric medicine and point out the capability of using E. foeminea to treat bacterial infections. Future studies are required to know the exact molecules as well as the mechanisms responsible for the genotoxicity of this plant. In vivo genotoxicity studies are recommend for assessment of the safety of using E. foeminea plant for therapeutic purposes.