Aims: To investigate the influence of polyphenols and plant extracts on the susceptibility of Escherichia coli to antibiotics. Methods and Results: Susceptibility of E.coli to antibiotics in the presence of extracts and polyphenols was estimated by the determination of the minimum inhibitory concentrations (MICs). To study gene expression, we used strains of E.coli carrying fusions between promoters of genes katG, sodA, iucC and structural beta-galactosidase gene. Treatment with polyphenols and some plant extracts significantly decreased the antibacterial effects of antibiotics, to a larger extent, ciprofloxacin. The most remarkable protective effect was observed for the extracts of Chamerion (Epilobium) angustifolium, Filipendula vulgaris, Tanacetum vulgare and Serratula coronata. These extracts increased the MICs of ciprofloxacin by four and more times. In case of kanamycin, extracts of Artemisia austriaca and Artemisia pontica increased MICs by four and eight times, respectively. Polyphenol quercetin also caused protective effect against ciprofloxacin, increasing the MIC by four times. A positive correlation was found between protective effects of polyphenols and extracts and their antioxidant activity. Conclusion: Medicinal plant extracts and polyphenols may protect cells of E.coli against antibiotic toxicity. Significance and Impact of the Study: The results of this study may be used to enhance the efficiency of antibacterial therapies.