Mitochondrial biogenesis (MB) is involved in the regulation of cellular energy metabolism, stress response, and survival. This review examines therapeutic approaches to acute kidney injury (AKI) that target MB, emphasizing clinical research findings and translational strategies in this field. AKI is a severe condition with high mortality and often leads to chronic kidney disease. AKI suppresses MB, resulting in mitochondrial dysfunction, oxidative stress, and further renal damage. Furthermore, studies have shown that ischemia-reperfusion-, sepsis-, and drug-induced AKI inhibit MB and subsequent kidney injury. Studies have shown that targeting MB through genetic and pharmacological interventions can alleviate AKI by restoring mitochondrial function and improving renal outcomes. Small molecule compounds, such as pyrroloquinoline quinone, ZLN005, and resveratrol, can enhance MB, offering potential therapeutic benefits. Nonetheless, further studies are needed to ensure efficacy across different models and mitigate related side effects. Future research should focus on optimizing drug design, understanding MB regulation, and conducting clinical trials to establish effective treatments for AKI.