Purpose: To analyze the risk of dental implant failure for patients with a history of antidepressant use through a systematic review and meta-analysis. Materials and Methods: An electronic search was performed up to June 2023 in three databases including PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials; data on the comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at patient level and implant level were performed. Results: Overall, 11 clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% CI = 1.75 to 3.39; P < .0001) and 2.44 (95% CI = 1.73 to 3.46; P < .0001) for the implant failure at patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other types of antidepressants had a higher risk of implant failure than those who were not on any antidepressants. Conclusions: The current review demonstrates that the use of antidepressants such as SSRIs may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to confirm this finding.