Major depressive disorder (MDD) and anxiety are prevalent psychiatric conditions often resistant to conventional pharmacological and psychotherapeutic interventions. Recent advances highlight the gut microbiota as a central regulator of mental health through the microbiota–gut–brain axis, influencing immune, endocrine, and neural pathways. Dysbiosis is associated with systemic inflammation, neurotransmitter imbalance, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, all contributing to mood symptoms. This chapter explores microbiota-targeted interventions-psychobiotics, prebiotics, omega-3 fatty acids, polyphenols, and sustainable diets such as the Mediterranean diet-as adjuncts or alternatives to antidepressants. Evidence from clinical and preclinical studies suggests these strategies improve depressive and anxiety symptoms, enhance microbial diversity, and offer fewer side effects. Future directions include multi-omics profiling, microbiome-informed precision psychiatry, and novel approaches such as designer probiotics and postbiotics, integrating sustainability with mental health care.