Saliva contains a diverse array of biomarkers indicative of various diseases. Saliva testing has been a major advancement towards non-invasive point-of-care diagnosis with clinical significance. However, there are challenges associated with salivary diagnosis from sample treatment and standardization. This review highlights the biomarkers in saliva and their role in identifying relevant diseases. It provides an overview and discussion about the current practice of saliva collection and processing, and advancements in saliva detection systems from methods to wearable oral devices. The review also addresses challenges in saliva diagnostics and proposes solutions, aiming to offer a comprehensive understanding and practical guidance for improving saliva-based detection in clinical diagnosis. Saliva diagnosis provides a rapid, effective, and safe alternative to traditional blood and urine tests for screening large populations and enhancing infectious disease diagnosis and surveillance. It meets the needs of various fields such as disease management, drug screening, and personalized healthcare with advances in saliva detection systems offering high sensitivity, fast response times, portability, and automation. Standardization of saliva collection, treatment, biomarker discovery, and detection between different laboratories needs to be implemented to obtain reliable salivary diagnosis in clinical practice.