The present study investigated the effect of the continentalic acid (CNT) isolated from the Aralia Continentalis against the LPS and E. coli-induced nephrotoxicity. The LPS and E. coli administration markedly altered the behavioral parameters including spontaneous pain, tail suspension and survival rate. However, the treatment with CNT dose dependently improved the behavioral parameters. The CNT treatment significantly improved the renal functions test (RFTs) and hematological parameters following LPS and E. coli-induced kidney injury. Furthermore, the LPS and E. coli administration markedly compromised the anti-oxidant enzymes and enhanced the oxidative stress markers. However, the CNT treatment markedly enhanced the anti-oxidants enzymes such as GSH, GST, Catalase and SOD, while attenuated the oxidative stress markers such as MDA and POD. The MPO enzyme is widely used marker for the neutrophilic infiltration, the LPS and E. coli administration markedly increased the MPO activity. However, the CNT treatment markedly attenuated the MPO activity in both LPS and E. coli-induced kidney injury. Furthermore, the CNT treatment markedly attenuated the NO production compared to the LPS and E. coli-induced kidney injury group. Additionally, the CNT treatment improved the histological parameters markedly (H and E, PAS and Masson's trichome staining) and protect the kidney from the inflammatory insult of the LPS and E. coli evidently. The comet assay revealed marked DNA damage, however, the CNT treatment markedly prevented the LPS and E. coli-induced kidney damage. The CNT treatment markedly enhanced the expression of Nrf2, while attenuated the iNOS expression in both models of kidney injury.