Major depressive disorder (MDD) represents a complex and challenging mental health condition with multifaceted etiology. Recent research exploring the gut-brain axis has shed light on the potential influence of gut microbiota on mental health, offering novel avenues for therapeutic intervention. This paper reviews current evidence on the role of prebiotics and probiotics in the context of MDD treatment. Clinical studies assessing the effects of prebiotic and probiotic interventions have demonstrated promising results, showcasing improvements in depression symptoms and metabolic parameters in certain populations. Notably, prebiotics and probiotics have shown the capacity to modulate inflammatory markers, cortisol levels, and neurotransmitter pathways linked to MDD. However, existing research presents varied outcomes, underscoring the need for further investigation into specific microbial strains, dosage optimization, and long-term effects. Future research should aim at refining personalized interventions, elucidating mechanisms of action, and establishing standardized protocols to integrate these interventions into clinical practice. While prebiotics and probiotics offer potential adjunctive therapies for MDD, continued interdisciplinary efforts are vital to harnessing their full therapeutic potential and reshaping the landscape of depression treatment paradigms.