Introduction: Morin hydrate (MH) is a bioflavonoid component of many fruits and vegetables. Our previous research demonstrated that MH provides neuroprotection in mouse models of acute restraint stress and sleep deprivation by attenuating hippocampal neuronal damage and enhancing memory. Based on these findings, our study investigated the role of MH in chronic stress-induced neuronal and biochemical perturbations in BALB/c mice. Methods: Male BALB/c mice were divided into 6 groups (n=6). Groups 1 and 2 received vehicle (10 mL/kg normal saline), groups 3-5 received MH (5, 10, 20 mg/kg IP), while group 6 received ginseng (25 mg/kg) daily and 30 minutes afterward were restrained in a plastic cylindrical restrainer for 14 days. Results: Immobility time in the forced swim test increased in the MH-treated group, indicating an antidepressant-like effect. Also, a reduction in frequency and duration of open arms exploration was observed in the elevated plus-maze (EPM) test in stressed mice, and administration of MH (5, 10, 20 mg/kg, IP) reversed these effects. An increase in blood levels of glucose, triglycerides, total cholesterol, and brain malondialdehyde and nitrite levels was observed in the stressed groups, which was reversed by MH. Furthermore, MH reversed the stress-induced reduction in HDL cholesterol and glutathione (GSH) levels and attenuated stress-induced alterations in the prefrontal cortex and hippocampus. Conclusion: Our findings suggest that MH attenuated chronic restraint stress-behavioral and biochemical perturbations, probably due to its capability to decrease oxidative stress and brain neuronal damage