To investigate the possible effects of alagebrium chloride (ALT-711) on oxidative stress (OS) process in aging hearts, we examined the role of ALT-711 in cardiac function and OS in the heart of aging rats. Increased mitochondrial DNA (mtDNA) deletion as well as nearly a twofold increase in advanced glycation end products (AGEs) accumulation were observed in aging heart, whereas only about 50% of the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were seen. However, after treatment with ALT-711, preserved cardiac diastolic function accompanied with reduced mtDNA deletion and about 30% of AGEs decrease was observed in aging hearts. In addition, ALT-711 can increase SOD and GSH-PX activities in aging hearts as well as in cultured cardiomyocytes. In conclusion, our study suggests that AGEs accumulation and the abnormalities in the OS in aging hearts can be attenuated by ALT-711, and this might be a novel underlying mechanism for ALT-711 in the treatment of cardiovascular diseases that develop with aging.