Heart failure is a common frequently-occurring disease, and it is the terminal stage of the development of various heart diseases. The pathogenesis is very complex and seriously endangers human health. A large number of studies have shown that Ca2+/Calmodulin dependent protein kinase II(CaMKII) plays an important role in the occurrence and development of heart failure. Traditional Chinese medicine has unique advantages and good prospects in the prevention and treatment of heart failure. Among them, there are many compound and their active ingredients can target and regulate CaMKII. This paper mainly expounds the mechanism of the CaMKII signaling pathway in the failing heart and the research progress of traditional Chinese medicine in preventing and treating heart failure by targeting the regulation of CaMKII signaling in recent years, in order to provide reference and expand ideas for clinical traditional Chinese medicine prevention and treatment in heart failure.