The herbal extract Yukmijihwang-tang (YMJ) has been widely used for centuries as an anti-aging herbal medicine in Asian countries. Among the various modified prescriptions of YMJ, YMJ derivatives (YMJd) were formulated to enhance memory retention. This study has three goals: 1) to quantitatively evaluate the memory-enhancing effect of YMJd using behavior tasks; 2) to use cDNA micro-array tools to identify candidate genes responsible for enhancing memory; and 3) to statistically evaluate the specific gene expression patterns using Real-time PCR. Memory retention abilities are addressed by the passive avoidance task with SD male rat. The retention time of the YMJd group was significantly delayed (ca. 100%), whereas with Ginkgo biloba and Soya lecithin treatment, this was only delayed 20% and 10%, respectively. The cDNA from the hippocampi of YMJd and rat control groups were applied to an Incyte rat GEM2 cDNA microarray. The microarray results showed that transthyretin and PEP-19 were abundantly expressed in the YMJd treated group. Importantly, PEP-19 is a neuron-specific protein that inhibits apoptotic processes. On the other hand, neuronal genes involved in neuronal death or neurodegeneration, such as pentraxin and spectrin, were abundantly expressed in the control group. The list of differentially expressed genes may provide further insight into the action and mechanism behind the memory-enhancing effect of herbal extracts of YMJd.