Vascular dementia (VD) is the second leading cause of dementia after Alzheimer's disease, accounting for 15% of dementia cases in China. Currently, clinical treatment for VD is merely symptomatic drug therapy, which cannot effectively prevent and treat VD. The endoplasmic reticulum (ER) and mitochondria are important organelles within cells, and their interaction plays a crucial role in maintaining cellular homeostasis. Recent studies have shown that ER-mitochondrial interaction is one of the significant pathophysiological factors in the development of VD, but the specific mechanisms remain unclear. Studying the pathogenic mechanisms of VD and exploring potential strategies targeting ER-mitochondrial interaction for VD treatment has important clinical significance. This article will review the molecular mechanisms of ER-mitochondrial interaction, the possible pathogenesis of VD, and the association between the two.