Periodontal disease is a chronic infectious condition mediated by dental plaque biofilms, characterized by the destruction of soft and hard tissues. Metal-organic frameworks (MOFs), a class of porous materials formed through the self-assembly of metal ions and organic ligands via coordination bonds, exhibit high specific surface areas, tunable pore structures, and multifunctionality. In recent years, MOFs have gained significant attentions in biomedical applications and show potential for periodontal therapy. This article reviews the latest research advances in MOFs for antibacterial therapy, drug delivery, and tissue regeneration, systematically analyzes their mechanisms, application potential, and translational challenges, and furtherly discusses future directions in the era of precision medicine.