<p>High-altitude acclimatization has always been a major concern to humans as it is directly related to the performance of travelers at high-altitude. However, acclimatization to high-altitude varies among individuals. The exposure of high-altitude to humans can cause moderate to severe symptoms like headache, vomiting, dizziness, fatigue, high-altitude cerebral edema, high-altitude pulmonary edema and if not treated timely may lead to death. These symptoms appear due to physiological, biochemical and metabolic changes and are generally assayed using blood, plasma or serum, but it is an invasive method and require technical expertise. Therefore, looking for an alternative biological fluid which is noninvasive and easily accessible will be advantageous. In this regard, saliva bears the potential to be an excellent biological fluid to assess high-altitude associated consequences as it offers a simple mode of collection, multiple sampling, noninvasive procedure, and also ensures the patient’s comfort. In the present review, we have emphasized the role of saliva, different collection methods, and salivary biomarkers responsive to high-altitude exposure. The review could be insightful for researchers as it contemplates saliva collecting strategies and diagnostic devices.</p>