The periodontium is a unique organ from the standpoint of building an organ-on-a-chip (OoC) since it is a system that is continually threatened by microorganisms, their noxious compounds, and antigenic components. At the same time, periodontal health depends on a balanced connection between the host and the bacteria in the oral cavity, which is a complex micro-ecological environment. The objective of this systematic review of in vitro studies is to revise the potential clinical application of OoC in periodontal diseases. PRISMA was used to guide this analysis. The review framework made use of several databases, including SCOPUS, PubMed/MEDLINE, SCIELO, and LILACS as well as the gray literature. This systematic review comprised seven studies. The clinical efficacy of OoC in periodontal diseases was observed in models of the gingival crevice for the research of periodontitis, periodontal medication analysis, the interaction of multiple microbial species, pH measurements in in situ-grown biofilm, testing antimicrobial reagents, evaluation of mucosal interactions with microorganisms, and a device for quantitative exploration of microorganisms. OoC has the potential to advance our understanding of periodontal diseases by providing a more accurate representation of the oral microenvironment and enabling the development of new treatments.