The endoplasmic reticulum is the site of protein synthesis, folding, post-translational modification, and Ca²⁺ homeostasis. Factors such as ischemia and hypoxia caused by acute ischemic stroke can induce the occurrence of endoplasmic reticulum stress (ERS). Mild ERS can restore the stability of the intracellular environment and enhance cell viability, but severe and continuous ERS can induce cell apoptosis or cause necrotic damage. This article mainly introduces the possible pathways to promote cell endogenous survival and the possible mechanism of ERS-induced cell death, and explores potential therapeutic targets for acute ischemic stroke.