Purpose: The aim of the present systematic review was to analyze the role of oxidative stress markers in patients with periodontal disease. Materials and Methods: A comprehensive search based on predetermined inclusion criteria was performed to identify studies evaluating oxidative stress markers in humans with and without periodontitis. The search included all studies up to February 2016 in the following databases: Ovid MEDLINE, Scopus, and Cochrane Library. Results: The initial search identified 2,523 entries. The final selection consisted of 16 articles. The characteristics of the studies and the outcomes measures were described. Conclusions: A clear relationship is suggested for oxidative stress and periodontitis. Besides the outcome patterns demonstrated, the findings of the present systematic review underline the necessity of methodological standardization. Future research focusing on disease susceptibility, predictive, prognostic and therapeutics aims need to be explored.