Increasing evidence from fluid biopsies suggests activation and injury of glial cells in epilepsy. The prevalence of clinical and subclinical seizures in neurodegenerative conditions such as Alzheimer's disease, frontotemporal dementia, and others merits review and comparison of the effects of seizures on glial markers in epilepsy and neurodegenerative diseases with concomitant seizures. Herein, we revisit preclinical and clinical reports of alterations in glial proteins in cerebrospinal fluid and blood associated with various types of epilepsy. We consider shared and distinct characteristics of changes in different age groups and sexes, in humans and animal models of epilepsy, and compare them with those reported in biofluids in neurodegenerative diseases. Our analysis indicates a significant overlap of glial response in these prevalent neurological conditions.