Acute kidney injury (AKI), a major health issue concerning ~50% of patients treated in intensive care units, generally leads to severe renal damage associated with high mortality rate. The application of nanotechnology for the management of AKI has profound potential of further development, providing innovative strategies for predicting the early onset and progression of renal disease and improving the treatment efficacy of the life-threating AKI. This review has comprehensively summarized the nanomedicines in the application of AKI diagnosis and emphatically discussed the unique potential of various nanotechnology-based drug delivery systems (e.g., polymeric nanoparticles, organic nanoparticles, inorganic nanoparticles, lipid-based nanoparticles, hydrogels etc.) in the treatment of AKI, allowing for improved therapeutic index by enhancing both efficacy and safety concurrently. These approaches may mechanically mitigate oxidative stress, inflammation, and mitochondrial and other organellar damage, etc. In addition, the combination of nanotechnology with stem cells-based therapy or gene therapy has been explored for reducing renal tissues damage and promoting kidney repair or recovery from AKI. The review provides insights into the synthesis, advantages, and limitations of innovative nanomedicine application in the early detection and effective treatment of AKI.