The essential oil obtained from <i>Dysphania ambrosioides</i> leaves (DAEO) has antifungal, antioxidant, and antimicrobial properties. This study investigated DAEO's chemical composition and its sleep-promoting effects via administration by inhalation in ddY mice. Ascaridole (35.5%) and <i>p</i>-cymene (47.2%) were the major components. To obtain insight into DAEO's effects on the central nervous system (CNS), ascaridole and <i>p</i>-cymene were evaluated for sedative activity by using the caffeine-treated excitatory mouse model. DAEO administration significantly decreased locomotor activity at all doses except 0.000 04 mg per 400 μL of triethyl citrate. Both ascaridole and <i>p</i>-cymene were highly effective in decreasing locomotor activity of excited mice by more than 50%. In addition, ascaridole and <i>p</i>-cymene prolonged the pentobarbital-induced sleeping duration by 42% and 77%, respectively. These effects were antagonized by coadministration of gamma-aminobutyric acid (GABA<sub>A</sub>)-benzodiazepine receptor antagonist, flumazenil (3 mg/kg), indicating that the GABAergic system mediates the sedative effect. Finally, inhaled ascaridole and <i>p</i>-cymene had no negative effect on motor coordination, as observed during the Rota-rod test. Therefore, via activation of the GABAergic system, ascaridole and <i>p</i>-cymene mediate the sleep-promoting effect of DAEO. The results further extend the knowledge on their use as potential promising natural products for the management of sleep disorders and CNS-related ailments.