Our objective was to investigate the effect of probiotic therapy on the profile of a psycho-emotional state and nature of neuro-immune-endocrine changes among patients with depressive disorders. Material and methods — The study involved 119 patients, diagnosed with a mild depressive episode (F32.0) or a moderate depressive episode (F32.1). The patients were split among two groups: Main Group, in which subjects were taking a probiotic medicine in addition to the standard therapy (Cipralex + Bac-Set Forte), and Comparison Group in which subjects were taking a placebo pill in addition to the standard therapy (Cipralex). The Control Group consisted of 30 subjects belonging to the health group 1 sensu the Order of the Ministry of Health care of the Russian Federation No. 869an of January 1, 2018. The examination included clinical and psychopathological, psychometric, and laboratory methods. Results — Patients with depressive disorders had dysfunction of cortisol and monoaminergic neurotransmitter systems, along with an increased content of proinflammatory cytokines and nitric oxide in their blood. As a result of the therapy with a probiotic medicine, in combination with an antidepressant, patients with depressive disorders had a statistically significant decrease in the levels of cortisol, dopamine, IL-6, TNF-, and NO, as well as a more pronounced reduction of depression symptoms, in comparison with the indicators of the patients who underwent standard therapy. Conclusion — Use of probiotics resulted in a more pronounced improvement of neuro-immune-endocrine indicators in study subjects, with subsequent improvement of their mental state – particularly, due to less obvious symptoms of depressive disorders.