The depressive disorder, a disabling disease that affects around 300 million people worldwide, is characterized by symptoms of depressed mood and anhedonia. The cause isn’t completely understood, however, some hypotheses, such as the neuroendocrine related to stress response, tries to justify the etiology. Nowadays, the chronic unpredictable mild stress (CUMS) model has been applied to induce depressive-like behavior in animals through environmental stressors. The usual strategy for treating depression requires a pharmacotherapy with antidepressants that usually involves a long latency period, treatment resistance and high adverse effects incidence. Thus, it is interesting to investigate new compounds with antidepressant potential. The (-)-α-bisabolol (BIS) is a sesquiterpene alcohol, which has a lipophilic character and biological activities such as neuroprotection. The aim of the present study was to evaluate the antidepressant effect of (-)-α-bisabolol in mice submitted to CUMS model. C57BL/6 male mice were divided in six groups in which animals, except for the control groups, were exposed to a 28 days experimental protocol that consists of exposure of random environmental stressors. On the 15th day forward, all the experimental groups received: saline (NaCl 0.9%, p.o), (-)-α-bisabolol (50 mg/kg, p.o), or Fluoxetine (10 mg/kg, p.o). At the end of the treatment protocol, the animals were submitted to behavioral tests: open field, forced swimming, tail suspension, sucrose preference, hole board and elevated plus maze. After 60 minutes, the animals were euthanized by decapitation, and the brain areas (hippocampus and prefrontal cortex) were dissected to investigate the effect of BIS regarding oxidative stress parameters, such as thiobarbituric acid reactive substance (TBARS) levels, nitrite/nitrate and reduced glutathione (GSH) content. The behavioral results showed that (-)-α-bisabolol administration for 14 days exhibited an antidepressant and anxiolytic effect, without altering locomotor activity, thus, showing no relaxing or psychostimulant action. In addition, it demonstrated an antioxidant effect reversing the CUMS-induced oxidative imbalance, especially on lipid peroxidation in the hippocampus. These unique data showed, for the first time, that (-)-α-bisabolol demonstrated an antidepressant and anxiolytic effect, and is promising for a therapeutic alternative for depressive disorders.