Herbal mixture extract is composed of Lavandula angustifolia, Chamaemeulum nobile, Aloysia triphylla, Thymus vulgaris, and Ocimum basilicum. Also, It has been reported that linalool, a major component of Lavandula angustifolia and Ocimum basilicum, has antioxidant, anti-inflammatory, neuroprotective effects, and so on. However, the effect of HME and linalool on behavior alterations induced by sleep deprivation has not been demonstrated yet. Several studies have demonstrated that sleep deprivation-induced memory impairment in animal models is well-known as a model of behavioral alterations. In the current study, we investigated the effects of HME (3, 10, 30, or 100 mg/kg, p.o.) and linalool (0.3, 1, or 3 mg/kg, i.p.) on cognitive and stress evaluation performance and biochemical parameters of sleep-disturbed mice. Spatial memory and learning memory were assessed by Y maze and passive avoidance test, respectively, and forced swimming test was also used to evaluate the anti-stress activity. After sleep deprivation induced by multiple platform method, HME and linalool significantly ameliorated spatial memory, learning memory, and stress activity. Linalool led to release serotonin, and reduce cortisol levels. In addition, HME resulted in release melatonin, and reduce cortisol concentrations in sleep disorder model. Our results suggest that HME and linalool have beneficial effects on behavioral alterations induced by sleep disturbance.