Purpose: To review the literature on the relationship of milk fat globule EGF and factor V/VIII domain containing (MFGE8) in periodontal Osteoimmunology and the clinical significance of MFGE8 in periodontal disease. Methods: Two reviewers carried out a computer-based literature search using PubMed, Scopus, and Web of Science to identify papers published up to November 2023. The keywords used in the investigation were "MFGE8" and various words related to periodontal disease (periodontal, periodontitis, gingival, gingivitis, gingiva, and periodontium). Results: MFGE8 plays a critical role in the etiology of periodontal disease via regulating pro-inflammatory cytokines and bone cells. In addition, MFGE8 may be applied as a diagnostic biomarker and a therapeutic target in periodontal disease. [ABSTRACT FROM AUTHOR]