The links between the oral microbiome, oral hyperpermeability, periodontitis, and metabolic syndrome (MetS) are good examples of the oral–systemic health connection. The oral microbiota is involved in host defense and metabolism. Oral dysbiosis disrupts periodontal homeostasis, increases the permeability of the oral mucosa, and triggers systemic inflammation, thus leading to MetS. On the other hand, metabolic disorders can change the environmental conditions in the oral cavity and exacerbate dysbiosis and periodontitis. Oral hyperpermeability is evidently a key player in this oral–systemic connection, allowing passage of oral bacteria, their by-products, and inflammatory mediators into the systemic circulation. It triggers the low-grade, chronic inflammation commonly seen in MetS and may exacerbate insulin resistance and other metabolic changes. Thus, periodontitis—a chronic inflammatory disease—is both a result and a cause of MetS. The classification of periodontitis as both a diagnostic marker and a treatment target in metabolic risk enhances the opportunity for the assessment and control of MetS. New-generation therapies targeting oral permeability and dysbiosis, such as barrier-strengthening agents, precision probiotics, and advanced antimicrobial agents, are potential strategies to address the oral–systemic health link. The concept of oral–systemic healthcare, incorporating both dental and medical care, is an emerging model of care delivery systems. Such strategies, including salivary risk management (SRM), targeted interventions, and patient education, may contribute to the enhancement of general health, particularly among individuals with or at risk of MetS.