In the present study, we found that oral administration of ginsenoside Rd and protopanaxatriol significantly suppressed the IS- or EC-induced depression-like behaviors, NF-κB activation, and NF-κB+/Iba1+ cell population in the hippocampus of mice, while the BDNF expression and CREB phosphorylation increased. The gene discussed is CREB1; the disease is depressive disorder.