Objective To investigate the protective effect of daidzein on mouse models of hydroquinone-induced dry age-related macular degeneration (AMD). Methods Sixty mice were randomly divided into a control group, a model group, a high-dose daidzein group and a low-dose daidzein group by the random number table method, with 15 mice in each group. Mice in the model group, high-dose daidzein group and low-dose daidzein group were given drinking water containing 0.8% hydroquinone, whereas mice in the control group were given conventional drinking water. Meanwhile, mice in the high-dose daidzein group were intragastrically administered 10 mg/kg daidzein dissolved in physiological saline, and those in the low-dose daidzein group were intragastrically administered 5 mg/kg daidzein dissolved in physiological saline. Mice in the model group and control group were given an equal volume of physiological saline by gavage at the same time. After 3 months, fundus retinal imaging was performed in mice of the four groups using the Micron Ⅳ retinal imaging system for small animals. The right eyeballs of the mice were harvested for transmission electron microscopy. The left eyeballs were enucleated for blood collection, and the isolated left eyeballs were subjected to enzyme-linked immunosorbent assay. Results Fundus retinal imaging showed that compared with the control group, the retinal thickness of the model group was decreased, the layered structure of the retina was damaged, and a large number of drusen were present in the Bruch's membrane, indicating the successful establishment of the dry AMD mouse model. Compared with the model group, the retinal thickness showed no significant change in the low-dose daidzein group, and drusen were still observable. In the high-dose daidzein group, the retinal thickness was significantly improved and close to that of the control group, with the irregular Bruch's membrane and rare drusen observed. Transmission electron microscopy of the fundus revealed that compared with the control group, the model group showed unclear retinal structure, decreased melanin granule content, and obvious deformation of the Bruch's membrane, suggesting the occurrence of dry AMD-like lesions. Compared with the model group, the low‑dose daidzein group showed no significant improvement in retinal structure, with the relatively regular Bruch's membrane and increased density of melanin granules. Compared with the low-dose daidzein group, the high‑dose daidzein group exhibited the regular Bruch's membrane and a higher density of melanin granules. Compared with the control group, the expression levels of malondialdehyde in ocular tissue were significantly increased in the model group, low-dose daidzein group and high-dose daidzein group, with a more marked increase in the model group. The expression levels of superoxide dismutase, glutathione and catalase in ocular tissue were significantly decreased in the model group, low-dose daidzein group and high-dose daidzein group, with a more pronounced reduction in the model group (P<0.05). The expression levels of glutathione and catalase in the high-dose daidzein group were significantly higher than those in the low-dose daidzein group (P<0.05). Compared with the control group, the serum expression levels of malondialdehyde were increased in the model group, low-dose daidzein group and high-dose daidzein group, with a more marked increase in the model group. The serum expression levels of superoxide dismutase, glutathione and catalase were decreased in the model group, and the serum expression levels of glutathione and catalase were decreased in the low-dose daidzein group (P<0.05). Compared with the model group, the serum expression levels of glutathione and catalase were increased in the low-dose daidzein group, and the serum expression levels of superoxide dismutase, glutathione and catalase were increased in the high-dose daidzein group (P<0.05). The serum expression level of catalase in the high-dose daidzein group was higher than that in the low-dose daidzein group (P<0.05). Conclusion Daidzein may exert a protective effect on mice with dry AMD by alleviating oxidative stress injury in retinal pigment epithelial cells.