Pancreatic ductal adenocarcinoma (PDAC) is a formidable global health concern with a dire prognosis, highlighting the critical need for early detection strategies. This systematic review delves into the potential of salivary biomarkers as a non-invasive means for identifying PDAC at its incipient stages. Saliva's proximity to the circulatory system enables the detection of tumor-derived biomolecules, making it an ideal candidate for mass screening. The analysis of three selected studies reveals promising candidates such as Neisseria mucosa, Fusobacterium periodonticum, polyamines, and specific long non-coding RNAs (lncRNAs). Notably, polyamines like spermine show potential in distinguishing PDAC, while lncRNAs HOX transcript antisense RNA (HOTAIR) and plasmacytoma variant translocation 1 (PVT1) exhibit superior sensitivity and specificity compared to traditional serum markers. However, challenges, including small sample sizes and a lack of validation, underscore the need for standardized diagnostic panels and large-scale collaborative studies. Advancements in nanotechnology, machine learning, and ethical considerations are crucial for harnessing the diagnostic potential of saliva. The review emphasizes the imperative for extensive clinical trials to validate salivary biomarkers, ensuring not only diagnostic accuracy but also cost-effectiveness, patient compliance, and long-term benefits in the realm of PDAC screening. Longitudinal studies are recommended to unravel temporal changes in salivary biomarkers, shedding light on disease progression and treatment response.