Pearl oyster shells comprise two layers, a prismatic and nacreous layer, of calcium carbonate. The nacreous layer has been used in Chinese medicine since ancient times. In this study, we investigated the effects of the extract from the nacreous layer of pearl oysters (nacre extract) on D-galactose-induced brain and skin aging. Treatment with nacre extract led to the recovery of D-galactose-induced memory impairment, as examined using the Barnes maze, novel object recognition, and Y-maze tests. A histological study showed that nacre extract suppressed D-galactose-induced neuronal cell death and the expression of B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), which causes apoptosis in the hippocampus. In addition, the expression levels of brain-derived neurotrophic factor, which counteracts age-related brain dysfunction, and nicotinamide adenine dinucleotide-dependent deacetylase (sirtuin 1), which delays aging and extends lifespan, increased after nacre extract treatment. Moreover, the nacre extract showed anti-aging effects against D-galactose-induced skin aging; it suppressed D-galactose-induced wrinkle formation, decreased skin moisture, decreased epidermal thickness, and destroyed collagen arrangement associated with aging. Furthermore, the nacre extract suppressed oxidative stress associated with aging in the brain and skin by upregulating the expression of catalase and superoxide dismutase. The expression level of the cellular senescence marker p16, which is induced by oxidative stress, was elevated in the hippocampus and skin epidermal layer of D-galactose-treated mice, and it was suppressed by the administration of nacre extract. These results show that the nacre extract can suppress D-galactose-induced aging by enhancing anti-oxidant activity and suppressing p16 expression. Thus, the nacre extract may be an effective anti-aging agent.