Andrographolide is the major compound found in the medicinal plant, (Burm.f.) Nees, which accounts for its medicinal properties. Both the plant extract and compound have been reported to exhibit potential cardiovascular activities. This review summarises related studies describing the biological activities and target mechanisms of and andrographolide in vivo and in vitro. The current evidence unambiguously indicated the protective effects provided by and andrographolide administration against myocardial injury. The intervention ameliorates the symptoms of myocardial injury by interfering with the inductive phase of a) inflammatory response mediated by nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signalling molecules; b) oxidative stress via activation of nuclear factor erythroid 2-related factor (Nrf-2) and reduction of enzymes responsible for generating reactive oxygen and nitrogen species; c) intrinsic and extrinsic mechanisms in apoptosis regulated by upstream insulin-like growth factor-1 receptor (IGF-1R) and peroxisome proliferator-activated receptor-alpha (PPAR-α); d) profibrotic growth factors thus reducing cardiac fibrosis, improving endothelial function and fibrinolytic function. In conclusion, and andrographolide possess therapeutic potential in the management of myocardial injury, which requires further validation in human clinical trials.