This review aims to systematically elaborate on the core mechanisms of ferroptosis in acute kidney injury (AKI), and to deeply dissect the molecular basis by which the guanosine triphosphate cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway inhibits ferroptosis through pathways such as regulating the coenzyme Q10 system and reconstructing the lipid metabolic network. On this basis, the article focuses on exploring therapeutic strategies targeting the GCH1-BH4 axis, including the latest research progress and application potential of GCH1 agonists, gene therapy, and nanomedicine delivery systems in experimental AKI models.