Sleep problems occur more frequently in individuals with autism spectrum disorder (ASD) than in typically developing individuals, and recent studies support a genetic link between ASD and sleep disturbances. However, it remains unclear how sleep problems may be mechanistically connected to ASD phenotypes. A longstanding hypothesis posits that an imbalance between excitatory and inhibitory (E/I) signaling in the brain underlies the behavioral characteristics of ASD. In recent years, emerging evidence has shown that regulation of the E/I ratio is coupled to sleep/wake states in wild-type animal models. In this review, we will explore the idea of altered E/I regulation over the sleep/wake cycle as a mechanism bridging sleep disruption and behavioral phenotypes in ASD.