Apoptosis is a complex and highly self-regulating form of cell death, which is an important cause of the continuous decline in ventricular function and is widely involved in the occurrence and development of heart failure, myocardial infarction, and myocarditis. Endoplasmic reticulum stress plays a crucial role in apoptosis-inducing. Accumulation of misfolded or unfolded proteins causes cells to undergo a stress response called unfolded protein response (UPR). UPR initially has a cardioprotective effect. Nevertheless, prolonged and severe ER stress will lead up to apoptosis of stressed cells. Non-coding RNA is a type of RNA that does not code proteins. An ever-increasing number of studies have shown that non-coding RNAs are involved in regulating endoplasmic reticulum stress-induced cardiomyocyte injury and apoptosis. In this study, the effects of miRNA and LncRNA on endoplasmic reticulum stress in various heart diseases were mainly discussed to clarify their protective effects and potential therapeutic strategies for apoptosis.