Background: The global crisis in shortage production and overuse of antibiotics resulted in the resurfacing of drug-resistant bacteria, posing a threat to the effects of conventional antibiotics. The medicinal plant Punica granatum L. (pomegranate) has been widely studied for its antimicrobial effects against bacteria, fungi, and helminths, because of the phytochemicals present in the different parts of the plant (leaves, petals, peels, seeds, and fruit). Studies show that pomegranate is effective against the potent gram-negative bacterium, Escherichia coli (E. coli). Different strains of E. coli are highly drug-resistant and multidrug-resistant. Hence, the objective of this paper is to determine the antibacterial efficacy of phytochemicals found in the different parts of pomegranate against E. coli. Materials and Methods: To review the antibacterial activity of Punica granatum L. against E. coli, online databases such as PubMed, and ScienceDirect were used to search for journals and studies published between 2013-present. Search terms include “Pomegranate”, “Punica granatum L.”, “Antibacterial”, “E. coli”, and “Extract”. And software named Zotero was used for the removal of duplicates. Conclusion: After the analysis, this review reveals that polyphenols, specifically flavonoids, and tannins, are the most common class of compounds present in many parts of pomegranate including the leaf, peel, and exocarp that exert antibacterial properties against E. coli.