OBJECTIVE To study the therapeutic effect of saikosaponins and paeoniflorin on rats with premenstrual dysphoric disorder(PMDD) model of liver Qi depression and the effect on neurotransmitters in hippocampal brain area. METHODS The PMDD rat model of liver Qi depression was prepared by the time-chosen chronic restraint stress method, and the depressive symptoms of rats were evaluated by the intervention of saikosaponins and paeoniflorin, the open field experiment and forced swimming experiment, and the changes of neurotransmitter levels in the hippocampal brain region of rats were detected by UHPLC-MS/MS target metabolomics. RESULTS The levels of 5-HT, Glu, GABA and NE in the hippocampal brain area of PMDD rats were significantly increased, and the levels of 5-HT, Glu, GABA, NE, DA and E were not statistically significant from those of the normal group after the intervention of saikosaponins and paeoniflorin. CONCLUSION Saikosaponins and paeoniflorin alleviates depression in rats with PMDD by regulating neurotransmitter levels, and it may be the pathway for the clinical treatment of PMDD with liver qi depression in the formulations of Bupleuri Radix and Paeoniae Radix Alba.