BACKGROUND: Acute kidney injury (AKI) is a common complication in clinical inpatients, and it continues a high morbidity and mortality rate despite many clinical treatment measures. AKI is triggered by infections, surgery, heavy metal exposure and drug side effects, but current chemical drugs often fall short of expectations for AKI treatment and have toxic side effects. Therefore, finding new interventions and treatments, especially of natural origin, is of remarkable clinical significance and application. The herbal monomer curcumin is a natural phenolic compound extracted from the plant Curcuma longa and showed various biological activities, including AKI. Furthermore, recent studies have shown that curcumin restores renal function by modulating the immune system and the release of inflammatory mediators, scavenging oxygen free radicals, reducing apoptosis and improving mitochondrial dynamics. However, curcumin has a low bioavailability, which limits its clinical application. For this reason, it is essential to investigate the therapeutic effects and molecular mechanisms of curcumin in AKI, as well as to improve its bioavailability for curcumin formulation development and clinical application. PURPOSE: This review summarizes the sources, pharmacokinetics, and limitations in the clinical application of curcumin and explores methods to optimize its bioavailability using nanotechnology. In particular, the therapeutic effects and molecular mechanisms of curcumin on AKI are highlighted to provide a theoretical basis for AKI treatment in clinical practices. METHODS: This review was specifically searched by means of a search of three databases (Web of Science, PubMed and Science Direct), till December 2021. Search terms were "Curcumin", "Acute kidney injury", "AKI", " Pharmacokinetics", "Mitochondria" and "Nano formulations". The retrieved data followed PRISMA criteria (preferred reporting items for systematic review) RESULTS: Studies have shown that curcumin responded to AKI-induced renal injury and restored renal tubular epithelial cell function by affecting multiple signaling pathways in AKI models induced by factors such as cisplatin, lipopolysaccharide, ischemia/reperfusion, gentamicin and potassium dichromate. Curcumin was able to affect NF-κB signaling pathway and reduce the expression of IL-1β, IL-6, IL-8 and TNF-α, thus preventing renal inflammatory injury. In the prevention of renal tubular oxidative damage, curcumin reduced ROS production by activating the activity of Nrf2, HO-1 and PGC-1α. In addition, curcumin restored mitochondrial homeostasis by upregulating OPA1 and downregulating DRP1 expression, while reducing apoptosis by inhibiting the caspase-3 apoptotic pathway. In addition, due to the low bioavailability and poor absorption of curcumin in vivo, curcumin nanoformulations including nanoparticles, liposomes, and polymeric micelles are formulated to improve the bioavailability. CONCLUSION: This review provides new ideas for the use of curcumin in the prevention and treatment of AKI by modulating the molecular targets of several different cellular signaling pathways.