Hypoxia disrupts oral homeostasis through multiple interconnected pathways, including interference with tooth germ development, impairment of salivary gland function and salivary buffering capacity, compromise of the oral mucosal barrier, imbalance in jawbone and alveolar bone remodeling, and alterations in the diversity and functionality of the oral microbiome. These disturbances collectively contribute to the onset and progression of oral diseases. Moreover, disruption of oral homeostasis may, in turn, affect systemic homeostasis, increasing the risk of disorders in other organ systems through mechanisms involving inflammatory mediator release and microbial translocation. Here, we systematically review the effects and underlying mechanisms of hypoxia exposure on oral homeostasis, and further explore the interconnections between hypoxia-induced oral dysregulation and systemic homeostatic imbalance. This review aims to provide a comprehensive understanding of the regulatory networks linking oral and systemic homeostasis under hypoxia, thereby offering potential insights for maintaining homeostatic balance.