Background: The treatment of periodontitis frequently begins with a non-surgical phase that includes scaling and root planing (SRP) and, on occasion, the use of systemic antibiotics. The goal of this review is to systematically evaluate the data concerning the effect of the concomitant administration of amoxicillin and metronidazole adjunctive to SRP in adults who are otherwise healthy., Methods: The PubMed-MEDLINE, Cochrane-Central, and EMBASE databases were searched to April 1, 2012, to identify appropriate studies. Probing depth (PD), clinical attachment level (CAL), bleeding on probing, and plaque index were selected as outcome variables. Based on the extracted mean values and number of individuals, changes in weighted means were calculated and a meta-analysis conducted., Results: The search yielded 526 unique titles and abstracts. Ultimately, 35 studies were selected, describing 28 clinical trials meeting the eligibility criteria. The full-mouth weighted mean change for PD showed an improvement of 1.41 mm. The full-mouth weighted mean change for CAL showed a gain of 0.94 mm., Conclusion: Systemic antimicrobial therapy using a combination of amoxicillin and metronidazole as an adjunct to SRP can enhance the clinical benefits of non-surgical periodontal therapy in adults who are otherwise healthy.