Acute kidney injury (AKI) is a serious clinical syndrome with high morbidity, elevated mortality, and poor prognosis, commonly considered a "sword of Damocles" for hospitalized patients, especially those in intensive care units. Oxidative stress, inflammation, and apoptosis, caused by the excessive production of reactive oxygen species (ROS), play a key role in AKI progression. Hence, the investigation of effective and safe antioxidants and inflammatory regulators to scavenge overexpressed ROS and regulate excessive inflammation has become a promising therapeutic option. However, the unique physiological structure and complex pathological alterations in the kidneys render traditional therapies ineffective, impeding the residence and efficacy of most antioxidant and anti-inflammatory small molecule drugs within the renal milieu. Recently, nanotherapeutic interventions have emerged as a promising and prospective strategy for AKI, overcoming traditional treatment dilemmas through alterations in size, shape, charge, and surface modifications. This Review succinctly summarizes the latest advancements in nanotherapeutic approaches for AKI, encompassing nanozymes, ROS scavenger nanomaterials, MSC-EVs, and nanomaterials loaded with antioxidants and inflammatory regulator. Following this, strategies aimed at enhancing biocompatibility and kidney targeting are introduced. Furthermore, a brief discussion on the current challenges and future prospects in this research field is presented, providing a comprehensive overview of the evolving landscape of nanotherapeutic interventions for AKI.