Shigellosis caused by Shigella is prevalent throughout the world with approximately 164.7 million cases, of which 163.2 million are in developing countries as per the World Health Organization report. In the current study the effect of a known Probiotic Lactic acid Bacteria (PLB) Pediococcus pentosaceus, a previously reported strain of PLB from our laboratory on gastroenteric pathogen – Shigella dysenteriae was studied and its mode of action was established. In agar diffusion tests PLB lysate showed larger inhibition zones of S. dysenteriae than a known Shigella susceptible antibiotic ampicillin which shows a better potentiality of PLB lysate over standard antibiotic. Further the effect of PLB lysate on Shigella dysenteriae lysis was confirmed by electrophoretic and microscopic study. PLB lysate at 250 μg/mL protein concentration inhibited ~70% of Shigella dysenteriae growth in vitro. A significant protection was observed against the cellular damage caused by Shigella dysenteriae lysate. Red blood cells and buccal cells protection against the lysis induced by Shigella dysenteriae lysate substantiated the cytoprotective role of PLB, thus PLB can be an effective natural agent against Shigella mediated infection.