Depression is a multifaceted psychiatric disorder mainly orchestrated by dysfunction of neuroendocrine, neurochemical, immune, and metabolic systems. The interconnection of gut microbiota perturbation with the central nervous system disorders has been well documented in recent times. Indeed, alteration of commensal intestinal microflora is noted in several psychiatric disorders such as anxiety and depression, which are presumed to be routed through the enteric nervous system, autonomic nervous system, endocrine, and immune system. This review summarises the new mechanisms underlying the crosstalk between gut microbiota and brain involved in the management of depression. Depression-induced changes in the commensal intestinal microbiota are majorly linked with the disruption of gut integrity, hyperinflammation, and modulation of short-chain fatty acids, neurotransmitters, kynurenine metabolites, endocannabinoids, brain-derived neurotropic factors, hypothalamic-pituitary-adrenal axis, and gut peptides. The restoration of gut microbiota with prebiotics, probiotics, postbiotics, synbiotics, and fermented foods (psychobiotics) has gained a considerable attention for the management of depression. Recent evidence also propose the role of gut microbiota in the process of treatment-resistant depression. Thus, remodeling of the microbiota-gut-brain axis using psychobiotics appears to be a promising therapeutic approach for the reversal of psychiatric disorders, and it is imperative to decipher the underlying mechanisms for gut-brain crosstalk.