Purpose. This work aimed to synthesize the results of recent meta-analysis focusing on polymorphism in inflammatory mediators and its relation with the risk of periodontitis development. Materials and Methods. A systematic search was conducted using databases for publications prior to October 2016. Three examiners extracted data from articles with a clear association between polymorphisms in the inflammatory mediator gene and the development of periodontitis through meta-analysis using the fixed or randomized statistical models to calculate the Odds Ratio with values of P < 0.05 considered significant. Results. A total of 13 meta-analysis articles with 25 polymorphisms in seven interleukins (IL-1A, IL-1B, IL-4, IL-6, IL-8, IL-10, and IL-18), three cellular receptors (Fcγ receptors: FCGR2A, FCGR3A, and FCGR3B), and five inflammatory mediators (COX-2, MMP-2, MMP-3, MMP-8, and MMP-9), with a total of 71,531 participants, approaching different classifications of the disease. Conclusion. The study demonstrated that polymorphisms in the IL-1A, IL-1B, IL-6, IL-10, MMP-3 (chronic form), and MMP-9 (chronic form) polymorphisms were significantly associated with the risk of developing periodontitis, whereas other polymorphisms in the IL-4, IL-8, IL-18, Fcγ, COX-2, MMP-2, MMP-3 (aggressive), MMP-8, and MMP-9 (aggressive) polymorphisms had no significant association with risk of developing periodontitis.