Abstract: Periodontal disease (PD) and obesity are characterized by a dysregulated inflammatory state. Both conditions trigger inflammatory and immune responses with an increase in proinflammatory cytokines such as Interleukin 6 (IL-6) and the release of inflammatory mediators such as C-reactive protein (CRP). Individuals with a high body mass index (BMI) present a chronic inflammatory state. The aim of the present study was to perform a systematic review of inflammatory markers (IL-6 and CRP) in obese patients with PD and their possible relationship by analyzing the levels of these markers. A digital literature search was performed in three databases—PubMed, SciElo and Medigraphic—through an advanced search for original articles, employing IL-6 and CRP in obese patients with PD, within a publication period from 2010 to 2021. PRISMA guidelines, the JADAD scale and a qualitative analysis of scientific evidence were performed using the Cochrane collaboration method and the RoB 2 assessment tool. Ten articles were included in this analysis with the variables recorded and associated with subjects with obesity and PD. Of the ten articles included, three analyzed IL-6 and CRP, four analyzed IL-6 and three analyzed CRP. In conclusion, and based on the available evidence, the aforementioned markers of inflammation demonstrate that there is a relationship between PD and obesity.