Present study aimed to evaluate the effects of Moodreal, a standardized saffron (stigma of Crocus sativus) extract, on alleviating stress and sleep disturbance induced by restraint stress (RS) in mice, and to compare those effects with L-theanine. Throughout high-performance liquid chromatography analysis, we found that Moodreal contained 23.49±0.05 mg/g of α-crocin. Oral administration of 5-20 mg/kg Moodreal for 2 weeks alleviated RS-mediated weight loss. In addition, Moodreal administration significantly restored blood melatonin levels, sleep latency, sleep duration, and movement convalescence time that were altered by RS. However, Moodreal decreased blood corticosterone and interleukin-6 levels induced by RS. In the cerebral cortex, Moodreal inhibited the decrease in γ-aminobutyric acid levels and the decrease in mRNA expression of corresponding receptors. Moreover, Moodreal blocked RS-mediated lipid peroxidation and improved the antioxidant capacities in the cerebral cortex. Histopathological observation indicated that Moodreal restored the number of viable neuronal cells reduced by RS in both the paraventricular nucleus and ventrolateral preoptic nucleus regions. Furthermore, administration with Moodreal reduced the number of c-fos positive neuronal cells in the paraventricular nucleus region increased by RS. In contrast, Moodreal inhibited the RS-mediated decrease in the number of c-fos positive neuronal cells of the ventrolateral preoptic nucleus region. The improvement effects of administrating 20 mg/kg Moodreal on RS-mediated stress and sleep disturbance was mostly superior than that of administering 100 mg/kg L-theanine. Taken together, present study suggests that a standardized saffron extract can be a promising nutraceutical effective in mitigating stress and preventing sleep disturbance.