Cardiomyocyte hypertrophy is the adaptive response of the heart to various physiological or pathological stresses. To combat this type of disease, more effective drugs are still needed. Wedelolactone is the main ingredient extracted from the medicinal plant Daylily and have effects such as immunomodulatory, anti-fibrosis, and anti-inflammation. However, the role and mechanism of Wedelolactone in myocardial hypertrophy are still unclear. Here, H9C2 cells were treated with Ang II to construct a cardiomyocyte hypertrophy cell model. We found Wedelolactone suppressed the survival of Ang II-induced cardiomyocytes. Wedelolactone further restrained the progression of Ang II-induced cardiomyocyte hypertrophy. Wedelolactone suppressed the oxidative stress of Ang II-induced cardiomyocytes, and restrained the apoptosis. Mechanically, Wedelolactone restrained the progression of Ang II-induced cardiomyocyte hypertrophy via Nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 pathway (Nrf2/HO-1 pathway). In summary, Wedelolactone attenuates angiotensin II-induced hypertrophy and apoptosis in cardiomyocytes. Wedelolactone attenuates angiotensin II-stimulated hypertrophy and apoptosis in cardiomyocytes. [ABSTRACT FROM AUTHOR]