Anxiety and depression, the most prevalent psychiatric disorders are co-morbid in nature affecting several people across the world. There is an increase in demand for complementary and alternative medicines, specifically herbal botanicals due to various side effects exhibited by conventional drugs. Herbal drugs mentioned in traditional medicines, face acceptance issues by the medical community due to lack of scientific data regarding their neurochemical pathways. Hence, there has been an increased interest in the quest to unravel the mechanisms of action of herbal psychotropics. With the advancements in “omic technologies” such as genomics, proteomics and metabolomics, research in the field of herbal psychopharmacology has gained momentum, providing a faster and informative platform for thorough evaluation of herbal drugs and formulations. In this article, we have reviewed several medicinal plants and their formulations that have shown potential anxiolytic and anti-depressant activities and have been screened for their biological mechanisms either at the gene, protein or metabolic level.