KCC2 has been shown to be important for neural maturation. We have shown that Porphyromonas gingivalis-derived lipopolysaccharide (P. g LPS) decreases KCC2 expression. We have also shown that oxytocin, Kamishoyosan, and Kamikihito restore the KCC2 decrease by P. g LPS treatment. However, the detailed molecular mechanism is still unclear. On the other hand, RAGE (receptor for advanced glycation end-products; AGE) was discovered as a receptor of AGE at first, it has been also reported as a receptor for LPS and oxytocin now. Therefore, we analyzed the relationship between P. g LPS and RAGE using PC-12 cells. SiRAGE Treatment reduced the expression of Tlr4, the receptor for P. g LPS, and canceled the KCC2 decrease by P. g LPS. In addition, P. g LPS treatment results in the nucleus localization of REST and MECP2 that bind to the transcriptional regulatory region of Kcc2, whereas siRAGE treatment inhibits the nuclear localization of REST and MECP2. Furthermore, Kamishoyosan treatment directly reduced the expression of Rage, and Kamikihito treatment increased the expression of Oxytocin, which is one of the ligands of RAGE. These results suggest that targeting RAGE can control the expression of KCC2, which is important for neurological maturation, and that Kamishoyosan and Kamikihito are potential therapeutic agents for neurological disorders.