Escherichia coli is a major global foodborne pathogen, infecting a wide range of animals and contaminating their meat products. E. coli, can lead to high morbidity and mortality with a huge economic loss especially if foodborne diseases are associated with multidrug resistant (MDR)- and multivirulent-producing pathogens. Due to the increased resistance to common antimicrobials used to treat livestock animals and human infections, the discovery of new and innovative nanomaterials are in high demand. Recently, metal oxides can be considered as effective inorganic agents with antimicrobial features. Hence, this study might be the first to evaluate the efficiency of metal oxide nanoparticles (MO-NPs) as novel antibacterial agents against MDR/multivirulent E. coli pathogens isolated from chicken meat. The occurrence of pathogenic E. coli was determined in fresh warm chicken meat parts (breast, thigh, liver and gizzard). Ninety-one of 132 (69%) chicken meat parts were Escherichia -positive with E. coli as the only species isolated. Out of identified 240 E. coli strains, 72.5% (174/ 240) were classified as MDR E. coli strains. Fifty-five profile patterns were obtained. From each pattern, one strain was randomly selected for further analysis of virulence and resistance genes. Extracted DNA was assessed for the presence of antibiotic resistance genes (blaIMP-7, blaIMP-25, blaTEM, blaSHV, blaOXA-2, tetA, aadA, and aac(3)- IV) and virulence genes (stx1, stx2, hlyA, eaeA, aggR, eltB, estIb, papA, afa and hlyD). Clustering analyses revealed that 10 E. coli harboring the highest number of virulence and resistance genes were shifted together into one cluster designated as cluster X. The average activities of zinc peroxide nanoparticles (ZnO2-NPs) were higher than that of zinc oxide nanoparticles (ZnO-NPs) and titanium dioxide nanoparticles (TiO2-NPs) by 20% and 29%, respectively. The anti-inflammatory activity of ZnO2-NPs in comparison with aspirin was assessed using membrane stabilization, albumin denaturation, and proteinase inhibition methods. Significant anti-inflammatory activity of ZnO2-NPs was achieved at concentration levels of 500–1000 μg/ml. It seems that MO-NPs are effective alternative agents, since they exhibited a competitive antibacterial capability against MDR/multivirulent-producing E. coli pathogens isolated from chicken meat. Hence, ZnO2-NPs are a promising nanoparticles-based material for controlling foodborne pathogens, thereby valued for food safety applications.