Foodborne pathogens especially bacteria cause a vast number of diseases which leads to a high mortality rate in humans. Conventional antibiotics have been employed in an attempt to eradicate these pathogens and this has led to the evolution of a multidrug resistant bacteria strain. Thus, a new genre of antibiotics is prepared by using nanoparticles as they show effective antibacterial capabilities. Biosynthesized nanoparticles are less toxic to humans as compared to chemically synthesized nanoparticles which are prepared using toxic precursors. They also exhibit enhanced antibacterial action along with the biomolecules that help in their formation. Among most metal oxides, magnesium oxide (MgO) nanoparticles show unique antibacterial properties due to their exclusive oxide vacancies and crystalline structure. The antibacterial activity of MgO nanoparticles synthesized using leaf extract is further enhanced by the presence of phytochemicals. The present work is a comparative study of the antibacterial activity of MgO nanoparticles synthesized using three different leaf extracts: (1) Amaranthus tricolor, (2) Amaranthus blitum and (3) Andrographis paniculata and their reaction towards Escherichia coli which is a gram negative, food borne pathogen. The results showed that the ~78 nm spherical shaped MgO nanoparticles synthesized from A. blitum, exhibited the highest antibacterial activity at 60 µL dosage. In addition, the effects of the characteristics of the MgO nanoparticles such as size, morphology, concentration, surface charge and phytochemicals on antibacterial mechanism were also discussed.