Background/Objectives: Oral biomarkers have gained attention as non-invasive tools for assessing systemic diseases due to their potential to reflect physiological and pathological conditions. This review aims to explore the role of oral biomarkers in diagnosing and monitoring systemic diseases, emphasizing their diagnostic relevance and predictive capabilities in clinical practice. Methods: This narrative review synthesizes the current literature on biochemical, immunological, genetic, and microbiological oral biomarkers, with a focus on their sources, types, and clinical applications. Key studies were analyzed to identify associations between oral biomarkers and systemic diseases such as cardiovascular diseases, type 2 diabetes mellitus, autoimmune disorders, and cancers. Results: Oral fluids, including saliva and gingival crevicular fluid, contain diverse biomarkers such as matrix metalloproteinases, cytokines, and genetic indicators. These markers have demonstrated potential in diagnosing and monitoring systemic conditions. Among others, elevated levels of salivary glucose and inflammatory cytokines correlate with diabetes progression, while vascular endothelial growth factor (VEGF) and salivary C-reactive protein might be applicable as indicators for periodontal disease and cardiovascular risk. Additionally, salivary biomarkers like amyloid-beta and tau are promising in detecting neurodegenerative disorders. Conclusions: Oral biomarkers might represent a transformative and point-of-care approach to the early management of systemic diseases; however, challenges in measurement variability, standardization, and validation remain.