Good quality sleep is essential for mental and physical health. Inadequate sleep impacts memory consolidation, learning and cognition, immune function, autonomic regulation, physical performance, and other vital functions. In many neurological disorders that are associated with sleep problems such as epilepsy and Alzheimer’s disease, changes in brain circuitry affect sleep-wake regulation mechanisms; this is reflected in anomalous sleep-wake architecture and usually accompanied by poor sleep depth. Thus, over many years, many approaches have been tried in humans and animal models with the goal of improving sleep quality. Unfortunately, each of those approaches comes with limitations or side effects. Thus, there is a need for a natural, safe, and low cost approach that overcomes many limitations to improve sleep and eventually the lives of individuals with sleep problems. Environmental temperature is one of the most important factors that affect sleep in humans and other animals. Studies have shown that the part of the brain governing thermoregulation is also involved in sleep-wake regulation. Even a mild change in environmental temperature can produce a significant effect on sleep. Thus, a better understanding of the sleep-thermoregulation interaction could lead to novel ways for treating many sleep disorders. As a first step on the translational pathway, experiments in animal models of disease conditions with disordered sleep are needed for investigating sleep–thermoregulation interactions and for devising and validating related approaches to enhance sleep quality before conducting them on humans. This dissertation explores and assesses the effect of changes in ambient temperature on sleep-wake architecture in control mice and epileptic mice, the latter from a model of temporal lobe epilepsy as an example of a disease model with disordered sleep. Then, based on the results of temperature effects on sleep in control and epileptic mice, different strategies are proposed and tested to modulate sleep through ambient temperature regulation in closed loop to improve sleep depth and regulate the timing of the sleep-wake cycle. The results presented in this dissertation demonstrate the feasibility of sleep enhancement and regulation of its timing and duration through manipulation of ambient temperature using closed-loop control systems. Similar approaches could foreseeably be used as more natural means for enhancing deep sleep in patients with epilepsy, Alzheimer’s, or Parkinson’s disease in which poor sleep is common and associated with adverse outcomes.