cardiovascular disease is the leading cause of death and disability worldwide. oxidative stress has been implicated in many types of cardiovascular disease. chronic cardiac stress conditions have been shown to be associated with an increase in myocardial oxidative stress following myocardial infarction, which in turn may lead to depressed contractile function, myocardial remodeling and heart failure. antioxidants play a protective role against oxidative stress damage through the removal of free radical intermediates and inhibition of oxidation reactions. an imbalance of free radicals and antioxidants results in cellular and sub-cellular damage. therefore, treatment with non-enzymatic antioxidants may provide protection against high levels of free radicals. we investigated, in three different studies, if treatment with antioxidants can protect the heart under conditions of oxidative stress. in the first study, a complex dietary supplement composed of numerous antioxidants and anti-inflammatory components was given to c57bl/6 mice that received a whole body radiation dose of 5 gy to investigate potential cardioprotective effects by measuring cardiac antioxidant status and apoptosis. in the second study, the same complex dietary supplement was given to thy1-gfp mice that received a radiation dose of 10 gy to the head to investigate the abscopal effect on the heart by measuring cardiac inflammation and fibrosis. in the final study, the potential cardioprotective effects of secoisolariciresinol diglucoside, a compound found in flaxseed, was investigated in a wistar rat model of pulmonary arterial hypertension by correlating cardiac functions with oxidative stress. we have shown that treatment with antioxidants may offer some protection to the heart in these models of oxidative stress though it is important to consider the extent of oxidative stress and when developing a antioxidant treatment protocol.