Alcohol use disorder (AUD) is caused by chronic alcohol consumption accompanied by neuroadaptive modulation in the brain. According to previous studies, ginsenoside, major components of Korean Red Ginseng (KRG), inhibits morphine-induced reinforcement and alleviate alcohol-induced hyperactivity. Despite existing study on the effects of KRG and ginsenoside on various abuse drugs, these effects on AUD have not been investigated yet. To evaluate the inhibitory effects of the major components of the KRG on alcohol-induced addictive behaviors in mice, we used oral self-administration (SA) and conditioned place preference (CPP). We also investigated the effects of ginsenosides on the alcohol-driven modulation of glutamatergic and DAergic system in the brain of mice using western blot analysis and enzyme-linked immunosorbent assay. In SA studies, treatment with ginsenosides significantly reduced alcohol-induced self-administration on a fixed-ratio 4 and progressive ratio schedule of reinforcement. In CPP studies, treatment with ginsenosides significantly inhibited alcohol-induced place preference. Furthermore, ginsenosides significantly reduced alcohol-driven expression level of glutamatergic- or DAergic-related protein in the mPFC of mice after CPP schedule injection. In conclusion, our findings suggest that ginsenoside Rb1 and Rg1 have inhibitory effects on alcohol-induced psychological dependence via modulating glutamatergic or DAergic system in different ways.