Background: Depressive disorder is a common psychiatric condition where suicidal tendency, adverse events of conventional drugs prompt us to find safer yet effective alternative solutions. Traditional Unani formulation Sharbat Ahmad Shahi is used as an antidepressant but needs to be validated along with its scientific mechanism of action. Serum Brain Derived Neurotrophic Factor (BDNF) level is nowadays considered an important biomarker of depression. Hence, we conducted a clinical study to evaluate the effect of Unani formulation in mild to moderate cases of depressive disorders. Methods: 20 diagnosed cases of depressive disorders (on DSM-V criteria) of mild to moderate intensity having Hamilton Depression Rating Scale score 8-18, were enrolled after informed consent procedure and given Sharbat Ahmad Shahi 20 ml twice daily for 6 weeks during the year 2019. Baseline and post treatment assessments were done using Hamilton Depression Rating Scale, Serum BDNF level and safety parameters. Result: Highly significant difference was observed between baseline and post treatment Hamilton Depression Rating scale scores and serum BDNF values (p<0.001). However, no significant correlation was observed between these two parameters. Serum BDNF Level was significantly better in cases with full remission in comparison to those who did not remit completely (p<0.05). No serious clinical adverse event was observed in study cases and safety parameters. Conclusion: Sharbat Ahmad Shahi is a safe and effective antidepressant that improves the serum BDNF level reversing the pathophysiology and hence it may be used as an alternative drug in mild to moderate depressive disorders.