Shigella dysenteriae continues to be a major health problem, which leads to death, due to diarrhoea and dysentery, predominantly in children below the age of 5. Bacterial invasion of the colonic epithelium leads to severe inflammation together with bacterial dissemination generates abscesses and ulcerations. Periplasmic copper, zinc super oxide dismutase of Shigella protects it from exogenous superoxide produced by host, during its invasion. Hence, in present study an attempt was made to study the effect of aqueous extract of Aegle marmelos on host and pathogen defence. Histology analysis of rat ileal loop showed the loss of virulence in aqueous extract of A. marmelos pre-treated Shigella and their intracellular survival was also decreased, where active component present in aqueous extract of A. marmelos was identified as imperatorin confirmed by UV absorption spectrum and HPLC. Increase in peripheral blood mononuclear cell viability and decreased in intracellular bacterial count along with transmission electron microscope analysis of imperatorin treated S. dysenteriae succumb to host oxidative stress. Loss of virulence is associated with attenuation of copper, zinc super oxide dismutase activity in Shigella, which was confirmed by using activity staining of bacterial cell lysate. Further, by performing docking analysis it has been proved that imperatorin present in aqueous extract of A. marmelos inhibited copper, zinc super oxide dismutase. From the above study, we concluded that Shigella succumb to oxidative stress (host defence) due to inhibition of copper, zinc super oxide dismutase (pathogen’s defence) by imperatorin, an active compound aqueous extract of A. marmelos.