Cognitive deficits are the most common phenotypes in normal aging, including the decline of episodic memory, spatial memory, and attention (Mosher et al. 2016). Others have reported that the major cause of cellular damage during ageing is due to the overproduction of reactive oxygen species (ROS), which are formed via reducing antioxidant defenses (Swomley et al. 2015). Selenium (Se) is a nutritionally essential trace element for human health, possessing diverse pharmacological activities (Rayman et al. 2012). Selenomethionine (SeMet), a major organic form of Se, has greater bioavailability and less toxicity than inorganic Se. Previous studies demonstrated that SeMet played a vital role in the synaptic plasticity and neural protection (Song et al. 2014). In this study, we investigate the protective effects of SeMet supplementation against D-gal-induced memory impairment in mice and explore the potential mechanisms related to the beneficial effects.