Aims <p>To evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on periodontal status through a systematic review and meta-analysis.</p> Methods <p>Nine databases were searched for clinical studies up to September 2024 to identify clinical studies comparing periodontal parameters such as probing depth (PD), clinical attachment level (CAL), marginal bone level (MBL), and gingival and plaque indices (GI and PI) between SSRI-users and non-users. Study selection, data extraction, and risk of bias assessment were performed independently by two authors. Random-effects meta-analyses of mean differences (MD) were performed. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of available evidence.</p> Results <p>Five cross-sectional studies, including a total of 1254 patients (54.15% females) and 13170 teeth, were included. The use of SSRIs was significantly associated with inferior MBL (MD, 0.10; 95% confidence interval, 0.01 to 0.20) compared to non-users. No significant differences were observed in PD, CAL, and GI between SSRI-users and non-users. The overall quality of evidence was low, and all studies presented a moderate risk of bias.</p> Conclusions <p>Based on a low level of available scientific evidence, the use of SSRIs has a marginal yet significant effect on MBL. However, there is no direct association between SSRIs usage and periodontal parameters such as PD, CAL, and GI. Nonetheless, further research is warranted.</p>