The persistence of stress responses or pain is a consequence of the body's reaction to adverse external stimuli, ultimately leading to maladaptation. The interactions between stress responses and pain challenge the body’s homeostasis. The review summarizes the research progress on the interrelated roles and mechanisms of glial cells in chronic stress and pain. Glial cell activation is one of the main features and driving factors of chronic stress-induced pain. Activated glial cells are involved in pain sensitization through a series of mechanisms, including the MAPK signaling pathway, chemokines, cytokines, and related receptors. Meanwhile, neuron-glial interactions regulate chronic stress-induced pain. The physiological and pathological changes in glial cells are closely related to the onset of some diseases induced by chronic stress.