There are obvious limitations in the traditional treatments for sleep-wake disorders like insomnia and excessive daytime sleepiness (EDS). The development of dual orexin receptor antagonists (DORAs) and orexin receptor agonists (ORAs), which target the orexin system, has introduced a revolutionary bidirectional regulatory strategy in this field. This article systematically reviews the progress in the research and clinical studies of these two classes of drugs. DORAs (e.g., suvorexant, lemborexant and daridorexant) promote sleep in a physiological manner by antagonizing both orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R), effectively improving sleep initiation and maintenance. They offer notable advantages, including the preservation of normal sleep architecture, minimal next-day residual effects, and a low risk of dependence, making them particularly valuable for elderly patients and those with neurodegenerative disease-associated insomnia. Conversely, ORAs (e.g., TAK-861) exert wake-promoting effects by activating OX2R, significantly alleviating core symptoms of daytime sleepiness and cataplexy, thereby representing a breakthrough in the etiological treatment of narcolepsy type 1. However, their clinical translation still faces challenges: DORAs exhibit interindividual pharmacokinetic variability and CYP3A4-mediated drug interactions, while ORAs require careful monitoring of potential safety concerns, such as neurological and urological side effects. DORAs and ORAs mark the advent of a new era in the precise and targeted modulation of sleep-wake disorders. Future directions include the development of novel formulations, the exploration of biased agonists, and the integration of precision medicine.