Ochratoxin A (OTA), commonly found in various foods, significantly impacts the health of humans and animals, especially their kidneys. Our study explores OTA's effects on the gut microbiota and kidney damage while examining how postbiotics offer protection. Using metagenomic sequencing, we observed that OTA increased the potential gut pathogens such as Alistipes, elevating detrimental metabolites and inflammation. Also, OTA inhibited the Nrf2/HO-1 pathway, reducing kidney ROS elimination and leading to cellular ferroptosis and subsequent kidney damage. Postbiotics mitigate OTA's effects by downregulating the abundance of the assimilatory sulfate reduction IV pathway and virulence factors associated with iron uptake and relieving the inhibition of OTA on Nrf2/HO-1, restoring ROS-clearing capabilities and thereby alleviating chronic OTA-induced kidney damage. Understanding the OTA-gut-kidney link provides new approaches for preventing kidney damage, with postbiotics showing promise as a preventive treatment.