The present study evaluated the antihypertrophic potential of the ethanolic extract of Boerhaavia diffusa (BDE), a well-known edible cardiotonic plant reported in Ayurveda against angiotensin II-induced hypertrophy in H9c2 cardiac myoblast cells. Markers of hypertrophy such as cell size, protein content and the concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were analysed for the confirmation of hypertrophy induction. Angiotensin II (100 nm) caused an increase in cell volume (69·26 (sd 1·21) %), protein content (48·48 (sd 1·64) %), ANP (81·90 (sd 1·22) %) and BNP (108·57 (sd 1·47) %). BDE treatment significantly reduced cell volume, protein content and the concentrations of ANP and BNP (P≤ 0·05) in H9c2 cells. The activity of various antioxidant enzymes and the concentration of reduced glutathione, which was lowered due to hypertrophy, were increased in BDE-treated cells. The BDE treatment also reduced intracellular reactive oxygen species generation, lipid peroxidation and protein carbonyls in cells. In addition, the expression patterns of NF-κβ and transforming growth factor β1 were found to be increased during hypertrophy, and their expressions were reduced on BDE treatment. In vitro chemical assays showed that BDE inhibits angiotensin-converting enzyme and xanthine oxidase in a dose-dependent manner with an estimated 50 % effective concentration (EC50) value of 166·12 (sd 2·42) and 60·05 (sd 1·54) μg/ml, respectively. The overall results clearly indicate the therapeutic potential of B. diffusa against cardiac hypertrophy, in addition to its nutritional qualities.