This study aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of the btulinum toxin-A (BT-A) in patiets with mood disorders. PubMed, Scopus, Web of Science, Cochrane Library and LILACS were searched without restrictions up to July 2022. The PICOS strategy was used for the selection of studies and risk-of-bias assessment was performed using Cochrane’s tool for RCTs. RCTs were included if they compared BT-A treatment on facial muscles in patients with mood disorders to placebo. After assessment of the full texts, seven studies were selected. Five studies had low risk of bias for the generation of random sequence and blinding of participants and professional domains. A total of four studies showed a low risk of bias for the allocation concealment and blinding of the evaluation of the domain results. The domain of selective reports showed a low risk of bias in all included studies. However, four studies presented a high risk of bias for the domain of other biases. The meta-analysis was based on the mean difference or standardized mean difference between the BT-A and placebo groups for each selected trial and revealed that the BT-A group showed a significant improvement in the symptoms of depression when compared to placebo. This study revealed that the BT-A application into mimic muscles of the upper third of the face improves the mood disorders, but it was not possible to guarantee whether the aesthetic benefits can contribute to reducing the severity of the depressive state.