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Introduction Acute mountain sickness (AMS) commonly occurs during rapid ascent to high altitudes and significantly affects the health and cognitive function of travellers and specialised personnel in high-altitude environments. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive, safe and portable neuromodulation technique with potential benefits for AMS. This protocol evaluates taVNS efficacy for AMS and associated cognitive impairment and explores its mechanisms via multiomics analyses.Methods and analysis This is a single-centre, randomised, double-blind, sham-controlled study involving ≥158 participants with AMS, who will be randomly assigned to receive either active or sham taVNS for five consecutive days. The primary outcome is the change in the 2018 Lake Louise AMS Score at 24 hours. Secondary outcomes are the Visual Analogue Scale for headache, Stanford Sleepiness Scale, Groningen Sleep Quality Questionnaire, resting heart rate, resting blood pressure, peripheral oxygen saturation, cerebral oxygen saturation, Corsi task score and the Picture Recall Subscale of the Wechsler Adult Memory Scale, which collectively assess symptom relief, physiological responses and cognitive function. The exploratory outcomes include faecal and urinary metabolomics.Ethics and dissemination All investigations performed in this study were reviewed and approved by the Ethics Committee of the Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences (reference number: P24013-PJ13). The findings will be disseminated through peer-reviewed publications, conference presentations and feedback for the study participants.Trial registration number http://itmctr.ccebtcm.org.cn/; number: TMCTR2024000642.