The influence of oral infections, especially periodontal disease, on systemic diseases has been extensively discussed in the literature. Because periodontal disease is a persistent infection, it promotes an inflammatory response. C-reactive protein is a marker for inflammatory reactions that is frequently studied, since elevated levels of this protein are related to coronary events. OBJECTIVE: The aim of this study was to investigate the effect of periodontal therapy on reducing the serum levels of C-reactive protein, by means of a systematic review of the literature and meta-analysis. MATERIAL AND METHODS: A systematic review of the English-language literature was conducted in the PUBMED-MEDLINE database, using the key words "periodontal disease", "C-reactive protein", "periodontal therapy" and "periodontal treatment", in accordance with the terms for Medical Subject Headings (MeSH), to evaluate the effect of periodontal therapy on C-reactive protein levels. A qualitative analysis of studies of randomized clinical trial design was performed using CONSORT, with subsequent meta-analysis. RESULTS: The literature search initially retrieved 46 potentially relevant studies available in the databases. From these, in accordance with the inclusion criteria, only 11 were selected, of which only 4 fulfilled the criteria of randomized clinical trial design. According to CONSORT, the studies evaluated generally presented good quality with regard to the criteria analyzed. Through meta-analysis, the reduction in mean levels of C-reactive protein (-0.231; p=0.000) after introducing periodontal treatment was estimated. The result was statistically significant, without evidence of heterogeneity between the studies (p=0.311). CONCLUSIONS: The findings indicated that non-surgical periodontal treatment had a positive effect with regard to reduction of the serum levels of C-reactive protein.