Antidepressant activity of curcumin (Cur), as a very well–known herbal product, has been investigated within this work. Two tautomeric forms of Cur–a and Cur–b in addition to the reference structure of Moclobemide (Moc) have been optimized first to evaluate molecular descriptors for ligands. Subsequently, monoamine oxidase–A (MAO–A) has been prepared as receptor for molecular docking (MD) simulation. Interacting systems of ligand–receptor have been very well determined in both of quantitative and qualitative aspects. The results indicated that both of Cur–a and Cur–b are good ligands for interactions with MAO–A even better than Moc, in which Cur–a is more favorable, But based on the interaction of Moc with flavin group of MAO–A, Cur could be employed as a complementary compound for antidepressant activity. All the interacting mechanism of ligand–receptor are very well recognized with this work.