Flavonoids are found in natural health products and plant-based foods. The flavonoid molecules contain a 15-carbon skeleton with the particular structural construction of subclasses. The most flavonoid’s critical subclasses with improved health properties are the catechins or flavonols (e.g., epigallocatechin 3-gallate from green tea), the flavones (e.g., apigenin from celery), the flavanones (e.g., naringenin from citrus), the flavanols (e.g., quercetin glycosides from berries, onion, and apples), the isoflavones (e.g., genistein from soya beans) and the anthocyanins (e.g., cyanidin-3-O-glucoside from berries). Scientific data conclusively demonstrates that frequent intake of efficient amounts of dietary flavonoids decreases chronic inflammation and the chance of oxidative stress expressing the pathogenesis of human diseases like cardiovascular diseases (CVDs). The endoplasmic reticulum (ER) is a critical organelle that plays a role in protein folding, post-transcriptional conversion, and transportation, which plays a critical part in maintaining cell homeostasis. Various stimuli can lead to the creation of unfolded or misfolded proteins in the endoplasmic reticulum and then arise in endoplasmic reticulum stress. Constant endoplasmic reticulum stress triggers unfolded protein response (UPR), which ultimately causes apoptosis. Research has shown that endoplasmic reticulum stress plays a critical part in the pathogenesis of several cardiovascular diseases, including diabetic cardiomyopathy, ischemic heart disease, heart failure, aortic aneurysm, and hypertension. Endoplasmic reticulum stress could be one of the crucial points in treating multiple cardiovascular diseases. In this review, we summarized findings on flavonoids’ effects on the endoplasmic reticulum and their role in the prevention and treatment of cardiovascular diseases.