Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of different variations in gene expression, providing this great advantage to the static measurement provided by genetic markers. The aim of this systematic review is to analyze the possible relationships between different epigenetic mechanisms and periodontal diseases, and to assess their potential use as biomarkers of periodontitis. A systematic search was conducted in six databases using MeSH and non-MeSH terms. The review fulfilled PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-analysis). 36 studies met the inclusion criteria. Due to the heterogeneity of the articles, it was not possible to conduct quantitative analysis. Regarding qualitative synthesis, however, it was found that epigenetic mechanisms may be used as biological markers of periodontal disease, as their dynamism and molecular stability makes them a valuable diagnostic tool. Epigenetic markers alter gene expression, producing either silencing or over-expression of molecular transcription that respond to the demands of the cellular surroundings. Gingival crevicular fluid collection is a non-invasive and simple procedure, which makes it an ideal diagnostic medium for detection of both oral and systemic issues. Although further research is needed, this seems to be a promising field of research in the years to come.