Background <p>Depression is a major global health issue. Recent studies suggest that botulinum toxin (BoNT/A), commonly used in aesthetic procedures, might have potential as an adjunct to traditional treatments for depressive symptoms. It is hypothesized that BoNT/A could influence neurochemical pathways to help alleviate depressive symptoms.</p> Methods <p>A systematic literature review was conducted focusing on Botulinum Neurotoxin Type A (BoNT/A) for depressive disorders. Primary studies published in English were included. Data were extracted on injection sites, dosage, adverse events, and outcomes. Statistical analysis included chi-squared tests and logistic regression to identify treatment predictors.</p> Results <p>Twelve studies were included, primarily targeting the glabellar region with BoNT/A injections. Approximately 71% of patients demonstrated reductions in depression symptoms. The chi-square test revealed a significant association between injection sites and depression improvement (<i>p</i> = 0.009). Higher doses of BoNT/A showed a marginally negative relationship with depression reduction (<i>p</i> = 0.098). Most adverse effects were mild, such as local site reactions and mild headaches, with no severe adverse events like suicidal ideation reported.</p> Conclusions <p>This review describes the possible use of BoNT/A as an adjunct therapy for depressive symptoms, particularly when targeting facial muscles. Further research is needed to optimize dosage and explore the neurobiological mechanisms involved to improve therapeutic outcomes.</p> Level of Evidence IV <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="http://www.springer.com/00266">www.springer.com/00266</a>.</p>