Targeting drugs to the heart is a challenging, due to its dynamic mechanical motions and large blood flow. Therefore, most common drug administration to treat heart disease is a systemic injection into blood vessel. However, this method has a few drawbacks, such as non-target delivery, low delivery efficiency, and so on. To overcome these problems, we show that the modified therapeutic protein or peptide with tannic acid, which is a flavonoid found in plants that adheres to extracellular matrix, elastin and collagen, improves their heart targeted delivery ability. In a rat model of myocardial ischemia-reperfusion injury, tannic acid-modified (TANNylated) proteins are mostly internalized at myocardium rather than adsorb on endothelial layers in blood vessels. As a result, TANNylated basic fibroblast growth factor significantly reduced infarct size and recover cardiac function.