The opportunistic Gram-negative anaerobic bacteria at the tooth-supporting system cause human periodontitis which is a persistent inflammatory disease. The anaerobic bacteria that reside there interact with the host's inflammatory responses to create a low-oxygen or hypoxic environment within the gingivitis-affected sulcus or periodontal pocket. To help tissues adapt to fluctuations in oxygen availability caused by pathology or natural occurrences, an oxygen-sensing mechanism within each cell and within each tissue is required, as well as its proper management. In this review article, the biological significance of hypoxia with regard to periodontal/oral cellular growth, epithelial barrier function, periodontal inflammation, and immunology has been described briefly.