Objective To investigate the efficacy of Oryzanol combined with Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets in the treatment of perimenopausal syndrome and its effect on endometrial thickness and neurotransmitters. Methods A total of 92 case of perimenopausal syndrome patients in Putian First Hospital during March 2019 to July 2021 were selected as studying object.They were divided into the control group and the intervention group by random number table method, with 46 cases in each group.The control group was given Oryzanol treatment, and the intervention group was given Oryzanol combined with Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets treatment.The curative effect, sex hormone levels, endometrial thickness, and neurotransmitter levels before treatment and one month after treatment were compared between the two groups, and the related adverse drug reactions were compared between the two groups. Results The total effective rate of the intervention group was higher than that of the control group, and the difference was statistically significant (P＜0.05).There was no significant difference in the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) between the two groups before treatment (P＞0.05).The level of E2 was higher than that of the two groups before treatment, and the difference was statistically significant (P＜0.05).The FSH and LH levels of the intervention group on 28 days of treatment were lower than those of the control group, and E2 level was higher than that of the control group, and the difference was statistically significant (P＜0.05).There was no significant difference in endometrial thickness, serotonin (5-HT) and norepinephrine (NE) levels between the two groups before treatment (P＞0.05).The thickness and 5-HT levels of the two groups were higher than those before treatment, and the NE level was lower than that of the two groups before treatment, and the difference was statistically significant (P＜0.05).The level of NE was higher than that of the control group on the 28th day of treatment, and the level of NE was lower than the level of the control group on the 28th day of treatment, and the difference was statistically significant (P＜0.05).There was no significant difference in the incidence of adverse drug reactions between the two groups (P＞0.05). Conclusion Oryzanol combined with Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets in the treatment of perimenopausal syndrome can significantly improve the endometrial thickness, sex hormone and neurotransmitter levels of patients, and has more significant clinical efficacy without increasing the risk of adverse drug reactions.