The microbiome residing in the human gut performs a wide range of biological functions. Recently, it has been elucidated that a change in dietary habits is associated with alteration in the gut microflora which results in increased health risks and vulnerability towards various diseases. Falling in line with the same concept, depression has also been shown to increase its prevalence around the globe, especially in the western world. Various research studies have suggested that changes in the gut microbiome profile further result in decreased tolerance of stress. Although currently available medications help in relieving the symptoms of depressive disorders briefly, these drugs are not able to completely reverse the multifactorial pathology of depression. The discovery of the communication pathway between gut microbes and the brain, i.e. the Gut-Brain Axis, has led to new areas of research to find more effective and safer alternatives to current antidepressants. The use of probiotics and prebiotics has been suggested as being effective in various preclinical studies and clinical trials for depression. Therefore, in the present review, we address the new antidepressant mechanisms via gut microbe alterations and provide insight into how these can provide an alternative to antidepressant therapy without the side effects and risk of adverse drug reactions.