In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA) in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs.