Drug-induced acute kidney injury (AKI), especially from exposure to antibiotics, has a high prevalence secondary to their frequent prescription. Typically, drug-induced AKI results from acute tubular necrosis or acute interstitial nephritis. While some risk factors for the development of AKI in individuals treated with antibiotics are modifiable, others such as concomitant drug therapies to treat comorbidities, age, and pre-existing chronic kidney disease are not modifiable. As such, there is an urgent need to identify strategies to reduce the risk of AKI in individuals requiring antibiotic therapy. Natural products, especially those rich in active constituents possessing antioxidant properties are an attractive option to mitigate AKI risk. Given that mitochondrial dysfunction precedes AKI and natural products can restore mitochondrial health and counter the oxidative stress secondary to mitochondrial damage investigating their utility warrants further attention. The following review summarizes the available preclinical and clinical evidence that provides a foundation for future study.