Background: Herbal medicines are preferred over chemical medications for a wide range of mental disorders such as depression. “ Monzej-e soda” is a polyherbal combination that has been used in Iranian traditional medicine for several years to cure different mood disorders with similar signs to depression. Traditional formulations should be reformulated to reach pharmacopoeial standards as modern medicines. Objectives: In this study, “ Monzej-e soda” was reformulated and its quality control and antidepressant evaluations were performed to present a standard and efficacious formulation. Methods: The aqueous extract of the mixture of Echium amoenum, Lavandula angustifolia, Melissa officinalis, Foeniculum vulgare, Ziziphus jujuba, Cordia myxa, Glycyrrhiza glabra, Fumaria parviflora, Adiantum capillus-veneris, and Alhagi spp. was dried with the spray drying method. Dried extract and various ingredients at different ratios were used to produce 13 experimental tablet formulations and several pre-and post-formulation tests were performed to select the best formulation. The formulation was evaluated physicochemically. The accelerated stability test was performed on the tablets, as well. Moreover, the antidepressant effect of tablets was evaluated by the forced swimming test. The serum levels of serotonin (5-HT), noradrenaline (NA), and brain-derived neurotropic factor (BDNF) were measured in rats. Finally, histopathological examinations were performed on the liver, kidney, and spleen. Results: Among different formulations, the best one was a combination of dried extract (490 mg), maltodextrin (189 mg), colloidal silicon dioxide (21 mg), and croscarmellose sodium (2%). The hardness, weight, friability, disintegration time, dissolution percentage, and total phenolic content were 6. 98 kg/cm2, 715. 76 mg, 0. 7%, 12. 0 min, 97. 46% in one hour, and 31. 4 mg/tab, respectively. No significant changes were seen in the product in the accelerated stability test. The polyherbal tablet produced significant antidepressant effects through the decrease in immobility time, which was mediated via an increase in NA and 5-HT levels. It had no effect on the BDNF level. In addition, tablets had no toxic effects on the liver, kidney, and spleen. Conclusions: “ Monzej-e soda” tablet can be considered a suitable antidepressant drug and used in patients after passing clinical trial tests.