Aim: The aim of this systematic review was to assess the clinical effect of adjunct antibiotics in the treatment of peri-implant diseases. Materials and Methods: An electronic systematic search was conducted by using the following databases: PubMed (Medline), Elsevier EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO-Dentistry and Oral Science Source, and WHO International Clinical Trials Registry Platform (WHOINT) from January 1980 to March 2020 (Registration in PROSPERO:CRD42018114147). Randomized controlled clinical trials with at least 10 patients with peri-implant diseases, treated with or without adjunct local or systemic antibiotics along with surgical or non-surgical therapies, and minimal three months follow up were included. Meta-analyses were performed to analyze weighted mean differences (WMD) in pocket depth (PD) reduction, radiographic bone level (RBL) gain, and odds ratio (OR) of treatment success. Subgroup analyses were conducted based on different diseases or type of antibiotics. Results: From 856 articles identified, 10 articles met the inclusion criteria were selected. Among them, 6 articles were included for meta-analysis. Adjunct antibiotics in the treatment of peri-implant diseases showed significant more PD reduction ( 3 mo: WMD = 0.56 mm, p = 0.001; 6 mo: WMD = 0.77 mm, p < 0.00001; 12 mo: WMD = 0.92 mm, p < 0.00001), RBL gain (WMD = 0.64 mm, p = 0.03) and treatment success ( OR = 1.74, p = 0.04) compared to the same treatment without adjunct antibiotics. Subgroup analysis showed the clinical benefit of antibiotics is especially significant in the treatment of peri-implantitis, not as much in peri-implant mucositis. Conclusion: From the current evidence, adjunct antibiotics provided additional beneficial effect up to 12 months in the treatment of peri-implant diseases, including PD reduction, RBL gain and treatment success.