Rice-memolin is a peptide generated by thermolysin digestion of rice bran that can improve cognitive decline. Rice-memolin corresponds to fragments of three rice protein sequences and appears to be resistant to gut proteases. In male ddY mice, rice-memolin improves cognitive decline induced by short-term high fat diet intake after oral administration in two behaviour tests, an effect inhibited by injection of methyllycaconitine (MLA), suggesting that rice-memolin acts through alpha7nAChR nicotinic receptors. Rice€'memolin also increases neurogenesis and expression of neurotrophic factors in the hippocampus and reduces blood glucose. Rice-memolin has no effect on hippocampal mRNA expression of inflammatory cytokines such as tumour necrosis factor-alpha, interleukin (IL)-1alpha, IL-1beta, and IL-6. Rice-memolin is the first rice-bran-derived peptide able to improve cognitive decline.