Background: Depression is a mental disorder characterized by low mood and loss of pleasure or interest in usual activities and often results in cognitive dysfunction such as impairment of learning and memory. For most of the synthetic antidepressants, severe defects such as narrow spectrum, adverse reactions, high drug price, and easy recurrence exist. Barley is one of the richest sources of antioxidants; therefore, we examined whether barley has an effect on depression, learning, and memory in a mouse model of reserpine‑induced depression. Methods: Mice were individually acclimated for 1 week and then treated with barley (200 mg/kg, p. o.) or/and fluoxetine (20 mg/kg, i. p.) for 4 weeks prior to reserpine treatment. Mice were then injected with a single dose of reserpine (2 mg/kg, i. p.) or vehicle (20 mg/kg, i. p.) and assessed for mouse behaviors 1 h prior to tests. Mouse behavior was examined in the forced swimming test, tail suspension test, hole‑board test, novel place/object recognition, social interaction test, spontaneous locomotor movement (SLMA), and stereotype movement following completion of the treatment protocol. Results: There was a significant antidepressant‑like effect in the forced swimming test among the barley group than in the reserpine‑treated group, and these decreases were significantly attenuated to a similar extent by treatment with fluoxetine. The effect of barley on the mean duration of immobility time was significantly attenuated in comparison with the reserpine group (P < 0.05). Moreover, the number of head pokes was significantly increased in the barley group in comparison with the reserpine or fluoxetine group. The mean duration of immobility time in the tail suspension test was significantly reduced in mice in the barley group in comparison with the reserpine group (P < 0.05). Furthermore, the social behavior test indicated that mice treated with fluoxetine have a significant increase in the distance covered by the mice toward familiar ones compared to the barley group, whereas the distance measured to the stranger mice was significantly increased among those who received fluoxetine with barley in comparison with the barley group alone. Finally, novel object recognition test, spontaneous locomotor movements (SLMA), and the stereotype movements showed that barley significantly decreased time spent on exploring the novel objects as well as in stereotype movements in comparison with the reserpine group. Conclusion: We conclude that barley can ameliorate depressive‑like effects. Taken together, these findings demonstrate that barley may be effective in treating patients with depression.