The kidney requires a significant number of mitochondria to perform essential functions such as waste removal, fluid and electrolyte regulation, and maintaining acid-base balance. Mitochondria provide the energy needed for these processes through various signaling pathways, including mTOR and AMPK, which activate the transcriptional co-activator PGC1α. Maintaining mitochondrial homeostasis is crucial for renal function, and dysfunction can lead to reduced ATP production, cellular alterations, and renal failure. Conditions like acute kidney injury (AKI) and diabetic nephropathy disrupt mitochondrial homeostasis, contributing to disease progression. Improving mitochondrial function has potential therapeutic benefits, and compounds that stimulate mitochondrial biogenesis have shown promise in restoring renal function in animal models. Additionally, inhibiting mitochondrial fission protein DRP1 might help mitigate ischemic renal injury by preventing mitochondrial fission. The review discusses the mechanisms of mitochondrial function, ATP production, antioxidant defenses, nutrient-sensing pathways, and the role of PGC1α in maintaining mitochondrial homeostasis. It also explores how diseases like AKI and diabetic nephropathy alter mitochondrial function and the potential for targeting mitochondrial energetics as a treatment strategy.The kidney requires a significant number of mitochondria to perform essential functions such as waste removal, fluid and electrolyte regulation, and maintaining acid-base balance. Mitochondria provide the energy needed for these processes through various signaling pathways, including mTOR and AMPK, which activate the transcriptional co-activator PGC1α. Maintaining mitochondrial homeostasis is crucial for renal function, and dysfunction can lead to reduced ATP production, cellular alterations, and renal failure. Conditions like acute kidney injury (AKI) and diabetic nephropathy disrupt mitochondrial homeostasis, contributing to disease progression. Improving mitochondrial function has potential therapeutic benefits, and compounds that stimulate mitochondrial biogenesis have shown promise in restoring renal function in animal models. Additionally, inhibiting mitochondrial fission protein DRP1 might help mitigate ischemic renal injury by preventing mitochondrial fission. The review discusses the mechanisms of mitochondrial function, ATP production, antioxidant defenses, nutrient-sensing pathways, and the role of PGC1α in maintaining mitochondrial homeostasis. It also explores how diseases like AKI and diabetic nephropathy alter mitochondrial function and the potential for targeting mitochondrial energetics as a treatment strategy.