Sleep deprivation (SD) not only directly affects an individual’s work efficiency but also negatively impacts various cognitive functions such as memory, attention, and learning as fatigue increases. Over the past few decades, numerous researchers have conducted lots of studies on the effects of SD on cognition, particularly memory. In this paper, we first review the effects of SD on memory function based on behavioral studies. Then, we further elaborate on recent advances in the physiological mechanisms of SD, including synaptic plasticity in structure and function, levels of excitatory and inhibitory neurotransmitters, and the expression of related synaptic protein signals. It has been observed that SD modulates the expression of synaptic protein signals and downstream signaling pathways by influencing changes in synaptic activities (such as dendritic spine density, synaptic connectivity strength, and the balance of excitatory and inhibitory synapses), ultimately affecting behavior. This review aims to provide insights into the research progress on the effects of SD on memory and its underlying mechanisms, providing a reference for future studies on sleep function and related mechanisms, as well as the development of strategies to mitigate memory deficits caused by SD.