In clinical medical practice, the applications of diagnostic and interventional procedures requiring iodinated contrast media (CM) administration have recently markedly increased. However, the intrinsic CM toxicity may lead to contrast-induced acute kidney injury (CI-AKI), particularly in patients with renal disease or diabetes. As successful therapy of CI-AKI is rather limited, effective strategies to prevent CI-AKI have become an insistent demand. The aim of this study was to evaluate the potential protective effects of the standardized extract of Ginkgo biloba leaves EGb761 against the pathophysiology of CI-AKI in a rat model. In this study, CI-AKI in rats was evaluated histopathologically and biochemically by measuring serum biomarkers of kidney function and tissue markers of oxidative stress, inflammation, tubular cell apoptosis and mitochondrial injury. Our results showed that CM administration led to several kidney morphological changes with alterations in serum and renal tissue parameters indicative of acute renal toxicity. These changes were moved to normality upon EGb761 treatment before CM exposure via integrated suppression of CM-induced renal tissue redox imbalance, inflammatory response, cell apoptosis activation and tubular cell mitochondrial damage. These findings demonstrated the nephroprotective effectiveness of EGb761 in alleviating CI-AKI pathophysiology through multiple effects. In conclusion, our study suggests a new therapeutic strategy for attenuating CI-AKI via administering EGb761 before CM use and may serve as an experimental basis for further studies to elucidate the promising clinical impact of EGb761 as a nephroprotective agent in patients at the risk of developing CI-AKI.