We recently reported the potential impacts of perilla seed oil (PO), a rich source of a-linolenic acid (ALA, C18:3, n-3), on cognitive function in healthy elderly Japanese individuals. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on brain functions in 49 healthy elderly Japanese individuals. PO group or the PO + ponkan powder (POPP) group for a 12-month randomized, double-blind, parallel-armed study. Taking a total of fifteen capsules daily for twelve months was not associated with any clinically significant side effects. From baseline to 12-months intervention, taking POPP significantly increased the cognitive index scores obtained by the three evaluation methods more than taking PO alone supplementation. The increased cognitive function observed in the POPP group was accompanied by increases in the levels of a-linolenic acid and docosahexaenoic acid in the erythrocyte plasma membranes and serum levels of brain-derived neurotropic factor (BDNF) and biological antioxidant potential. Our results demonstrate that a 12-months intervention with PO plus nobiletin-rich ADPP supplementations enhances serum BDNF and the antioxidant potential and may improve the age-related cognitive decline in healthy elderly individuals by enhancing the erythrocyte w-3 fatty acid levels.