The number of people travelling to high-altitude areas or participating in mountain sports is increasing. For individuals visiting such terrains for the first time, the lack of adaptation to the hypobaric hypoxic environment can lead to the deterioration of gastrointestinal function and barriers. In more severe cases, this lack of acclimatisation may lead to acute high-altitude illness. At present, the prevention and treatment of these issues primarily revolve around strategies such as descending to lower altitudes, oxygen supplementation, and medication. However, the available intervention measures to prevent health problems resulting from high-altitude environments remain limited. In this review, we discuss common altitude-related illnesses, including gastrointestinal problems. Moreover, we explore the potential of commonly used medications and dietary supplements in alleviating altitude-related issues. This review can provide a basis for future research on modulating the gut microbiota for mitigating high-altitude illness.