In conclusion, the present study demonstrated for the first time that muscone significantly inhibits Ang II-mediated myocardial hypertrophy in mice, and it predicted for the first time the affinity and potential binding sites of muscone with P38, ERK, and JNK in the MAPK pathway as well as SMAD2, SMAD3, SMAD4, and SMAD7 in the TGF-β/SMAD pathway by molecular docking analysis. This evidence concerns the gene SMAD4 and cardiac hypertrophy.