Background: This study aimed to evaluate the antibacterial effects of Punica granatum extract on such pathogenic bacteria as Staphylococcus aureus and Escherichia coli. Materials and methods: The samples from 130 patients with skin infections in Baghdad, Iraq, aged between 15 and 60 over years were collected for this study. The study collected. Each isolate was positively identified using morphological, cultural, and biochemical assays as detailed in the reference. The P. granatum peels were air-dried and powdered. Then 25g were extracted using 500 mL of water and ethanol on Soxhlet equipment for 72 hours. The extracts were then cooled, filtered, and concentrated at 40oC to get the crude extract; it was kept at four degrees centigrade in dark vials until use. The extracts were tested for the presence of alkaloids, tannins, flavonoids, glycosides, as well as steroidal terpenes. The efficacy of antimicrobial effects was calculated using well-diffusion techniques on Muller Hinton Agar (MHA). The plates were injected with a standardized suspension of the test isolates against McFarland tube 0.5. Five wells, each measuring five millimeters in diameter, were evenly spaced out using a sterile standard core borer. The well bottoms were sealed with sterile molten nutritional agar to prevent the extract from leaking out from beneath the agar. The aqueous and ethanolic crude extracts dissolved in DMSO served as positive controls, while sterile water and 10% DMSO served as negative controls. Each extract was diluted to a final concentration of 50, 100, or 200mg/ml, and 25 ml was added to the appropriate well on the infected plate. The plates were then incubated for 24 hours at 37 degrees Celsius. A millimeter-calibrated ruler was used to measure the size of the resultant inhibitory zones. The zone of inhibition of the test microorganisms at that dose was calculated as the mean of three measurements. Results: Clinical isolates of E. coli and S. aureus were inhibited by pomegranate extracts at a concentration of 200mg/ml compared to other concentrations, and this extract concentration showed a non-significant difference with chloramphenicol (P<0.01). The study revealed that pomegranate peel extract significantly reduced E. coli levels in feces and increased survival rates in rats. On the first day, E. coli concentrations were much higher in the control group (G2) compared to the treatment group (G3). By day 6, all rats in the control group had died, while all rats in the treatment group survived. Pomegranate peel extract shows notable antibacterial properties, impacting bacterial membrane permeability and cell survival. The variation in extract composition affects its efficacy. Conclusion, Pomegranate peel extract significantly reduced E. coli levels and improved survival rates in rats. On day 6, all rats in the control group died, while all in the treatment group survived. The extract's antibacterial effects and impact on bacterial membranes highlight its potential as a therapeutic agent.