Objective To investigate the effect of leonurine on podocyte injury induced by high glucose through the regulation of ferroptosis. Methods The mouse podocytes were divided into four groups: the normal control group, the high glucose group, the high glucose + leonurine group, and the high glucose + leonurine + Erastin (ferroptosis inducer) group. The survival rate of the podocytes was assessed using the cell counting kit-8 (CCK-8) assay. The death of the podocytes was determined using the lactate dehydrogenase (LDH) cytotoxicity assay kit. Lipid peroxidation was measured using a lipid peroxidation probe and a malondialdehyde (MDA) assay kit. The content of glutathione (GSH) was measured using a GSH assay kit. The concentration of iron was detected using an iron colorimetric assay kit. The protein levels of the ferroptosis markers GPX4, TFR1, and ACSL4 were measured using Western blot analysis. Results In comparison to the normal control group, the high glucose group exhibited significant podocyte injury, elevated lipid peroxidation, decreased GSH content, increased iron concentration, downregulated GPX4 protein level, and increased TFR1 and ACSL4 protein levels (P＜0.01). In comparison to the high glucose group, the high glucose + leonurine group showed a significant decrease in podocyte injury, a reduction in lipid peroxidation, an increase in GSH content, a decrease in iron concentration, an upregulation of GPX4 protein levels, and a decrease in TFR1 and ACSL4 protein levels (P＜0.01). In comparison to the high glucose+leonurine group, the high glucose + leonurine + Erastin group showed a significant increase in podocyte injury, lipid peroxidation, and ferroptosis (P＜0.05). Conclusion Leonurine demonstrates ameliorative effects on podocyte injury induced by high glucose through the inhibition of ferroptosis