Aims: This study was conducted to evaluate the genotoxic effects of fruit and leaf ethanolic extracts of Ecaballium elateruim on clinical and reference strains of E. coli (E. coli ATCC 25922). Methodology: The genotoxic effects of fruit and leaf ethanolic extracts were determined by using enterobacterial repetitive intergenic consensus (ERIC-PCR) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Results: The results showed an alteration in DNA and protein profiles of both tested Escherichia coli strains treated with fruit and leaf extracts compared with untreated control. The alterations ranged between decreased or increased intensity of some bands, absence or appearance of new amplified fragments. Moreover, increased concentrations of E. elaterium extracts and increased time intervals seems to yield a more profound increase in total protein concentrations in both tested E. coli strains.