Abstract: Enteropathogen-caused diarrhea in Latin America is prevalent in children. The increasing number of reports on antibiotic resistance of Shigella in several parts of the world, recommend the search of alternative therapies. The use of natural inhibiting substances is an alternative treatment. The current study assessed in vitro antimicrobial activity of Aqueous Extracts (AE) from pomegranate peel (Punica granatum L.) against clinical isolates of Shigella using the following techniques; agar diffusion, Minimum Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC) and bactericidal activity (death curve). Phytochemical analysis revealed the presence of active inhibitors in the peel including phenolics and flavonoids. The AE from the pomegranate peel showed highest inhibition against Shigella flexneri with a MIC of 250 μg mL-1 and a MBC of 500 μg mL-1. The death curve decreased 3 log units after 4 h indicating a bactericidal effect and photomicrographs showed the loss of cell wall integrity. AE activity was related to the higher content (46%) of total phenolic compounds.