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Abstract: Objective: This systematic review and meta-analysis considered the results of randomized controlled clinical trials (RCTs) to evaluate the efficacy of systemic or local antibiotics therapy on peri-implantitis. Methods: Two independent reviewers screened publications from three electronic databases to include randomized controlled clinical trials meeting all the inclusion and exclusion criteria. A meta-analysis was performed to evaluate the weighted mean differences in survival rate (SR), changes in pocket probing depth (PPD), bone level (BL), and clinical attachment level (CAL). The study cohorts were defined as antibiotics and control groups with subgroups for analysis. Main results: Seven studies including 309 patients and 390 implants were considered. Within the limitations of this review, patients in the antibiotic groups exhibited significant improvements in PPD. Subgroup analysis indicated that the administration of systemic antibiotics or the use of antibiotics in nonsurgical treatments did not result in a significant alteration in BL. Conclusions: Within the limitations of this review, it was established that the addition of antibiotics can ameliorate PPD and SR in the treatment of peri-implantitis, whether through surgical or non-surgical approaches, and also show moderate performance regarding BL and CAL. Considering the lack of application of new technologies in control groups and the hardship of assessing the potential risks of antibiotics, careful clinical judgment is still necessary.