DMBA (7,12-dimethylbenz[a]anthracene) is a polycyclic aromatic hydrocarbon (PAH) known to cause tumors in rats. Selenium is an essential element with physiological nonenzymatic antioxidant properties. Because of the health problems induced by many environmental pollutants, many efforts have been undertaken in evaluating the relative antioxidant potential of selenium and synthetic organoselenium compounds. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (1-isopropyl-3-methylbenzimidazole-2-selenone [Sel] and 1,3di-p-methoxybenzylpyrimidine-2-selenone [Sell]) in the determined doses. The protective effects of novel synthetic organoselenium compounds (Sel and Sell) against DMBA-induced changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and total glutathione (GSH) and malonedialdehyde (MDA) levels of rat heart and brain were investigated. It was determined that Sel and Sell fully or partially restored enzyme activity. It was also found that lipid peroxidation was also decreased in Sel and Sell treated groups. Consequently, it was determined that novel synthetic organoselenium compounds (Sel and Sell) provided protection of antioxidant activity, and protection against lipid peroxidation measured as MDA in Sel and Sell treated groups was provided by novel synthesized organoselenium compounds. The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rats was rationalized.