The endoplasmic reticulum (ER) is a principal organelle for folding, post-translational modifications and transport of secretory, luminal, and membrane proteins. ER stress is a condition induced by the accumulation of unfolded or misfolded proteins owing to a variety of physiological and pathological phenomena. To overcome the deleterious effects of ER stress, unfolded protein response (UPR) is initiated to translocate and remove the misfolded and accumulated proteins. Plenty of evidence shows the correlation between ER stress/UPR and the pathology of inflammatory disease. Periodontal disease is a chronic inflammatory disease characterized by the irreversible destruction of periodontal tissues, which associates with the onset and progress of several systemic diseases. Periodontopathic bacterium and pro-inflammatory mediators play a pivotal role in the progress of periodontal disease. Besides, cigarette smoke has long been associated with periodontal disease. As an inflammatory disorder of the periodontium, periodontal disease is highly related to ER stress. In this review, we provide an overview of the pathophysiological effect of ER stress on periodontal disease through five aspects as follow: ER stress and periodontal tissue remodeling, including both soft tissue and hard tissue; ER stress and the inflammation; ER stress and systematic effect during the periodontal disease; last but not least, ER stress and the autophagic apoptosis in cells.