<p>Hypoxia–ischemia plays a role in the physiological and pathological processes of various diseases and presents a common challenge for humans under extreme environmental conditions. Neurons are particularly sensitive to hypoxia–ischemia, and prolonged exposure may lead to irreversible brain damage. The primary mechanisms underlying this damage include energy depletion, mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Mitochondria serve as primary organelles for adenosine triphosphate (ATP) production, and mitochondrial dysfunction plays a crucial role in mediating hypoxic pathophysiological processes. Hypoxic–ischemic preconditioning (H/IPC) is an endogenous cellular protective mechanism that reduces the damage caused by lethal hypoxic stressors. In this review, we summarize the potential role of H/IPC and its protective effects on mitochondrial quality control and function. This perspective offers a new approach for treating diseases caused by hypoxia–ischemia.</p>