Pharmacological inhibition of NRF2 with ML385 partially attenuated the protective effects of ZXSZF.<h4>Conclusions</h4>ZXSZF alleviates podocyte injury in DKD and its renoprotective effects are associated with modulation of ferroptosis-related processes involving the NRF2/SLC7A11/GPX4 pathway. Here, GPX4 is linked to diabetic kidney disease.