The endoplasmic reticulum has emerged as a modulator that is essential for cellular homeostasis
and human health. It is an extensive membranous organelle that acts as a hub for the
physiological and pathological processes. In recent years, it has become a topic of interest in
studies on the relationship between endoplasmic reticulum homeostasis and system diseases.
Periodontal disease is a prevalent chronic disease that affects tooth-supporting tissues, initiated
by the interaction between pathogenic bacterial infection and immune defence and resulting
in tooth loss. The endoplasmic reticulum participates in the responses to the fluctuating
microenvironments in periodontal pathogenesis and regulates periodontal homeostasis. In
this review, we present an overview of the significance of endoplasmic reticulum regulation
as a multidimensional mediator in periodontal disease and highlight the potential strategies
for periodontal regeneration.