The aim of this study was to determine if the isoflavones from Sophorae fructus (SISO) have potential clinical benefit in hormone replacement therapy (HRT) for the treat ment of menopausal signs, such as the levels of total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and follicle stimulating hormone (FSH). An additional aim was to present the potential antioxidant effect of SISO in a microglial cell line. For the animal model, the ovaries were removed from adult rats and the indicators of menopause were measured at the pre- and post-administration time points. Although no statistically significant correlation was found, SISO tended to decrease the TC level (p=0.15) and the FSH level (p=0.36), but to increase the HDL level (p=0.303).SISO (< 5${mu}g$/mL) also exerted antioxidant activity on BV-2 microglial cells by inhibiting lipopolysaccharide-induced nitric oxide. This cytoprotective effect was confirmed by trypan blue staining, which was used to test for cellular damage from H$_2O_2$. In conclusion, this study highlights the anti-menopausal and antioxidant effect of SISO in an ovariectomized rat model, as well as in microglial cells, and provides new clinical targets for the screening of phytoestrogens as potential candidates for HRT in menopausal women.