Natural torpor is a seasonal adaptation that ensures very low energy expenditure to survive periods of harsh conditions. The brains of hibernating mammals can survive prolonged periods with a low body temperature and low energy supply. Moreover, they exhibit marked changes in neuronal morphology, function, and network connectivity during the torpor-arousal transition. Intriguingly, these changes are fully restored soon after arousal under suitable conditions, with no apparent signs of injury. Their distinct phenotypic plasticity reflects a remarkable capacity for neural regrowth and reorganization. To some extent, the brains of hibernating mammals possess the ability to reset upon arousal. Their natural advantages and unique neural plasticity traits hold great translational promise and value for various brain health application scenarios. In addition, the brains of hibernating mammals represent ideal model systems for exploring the foundations of memory engrams. However, the exact operating principles involved in the brains of hibernating mammals, and their profound impacts on brain function, remain enigmatic. Thus, dissecting the neurobiological underpinnings of these features of the brains of hibernating mammals and their neural plasticity traits during the torpor-arousal cycle could not only shed light on the mysteries of memory but also facilitate the translation of natural torpor into practical implications for human health. Herein, we focus specifically on this topic, as well as on identifying the possible difficulties and challenges that lie ahead, with the hope of 1 day achieving therapeutic synthetic torpor in humans.