BACKGROUNDOchratoxin A (OTA) is a mycotoxin that contaminates grape‐based products and is extremely harmful to the health of the host. It is effectively removed by yeast during the fermentation of wine, whereas the removal mechanism of OTA remains unclear. Therefore, the present study aimed to investigate the removal mechanism of ochratoxin A by yeast and to evaluate the safety of its degradation products.RESULTSCryptococcus albidus (20‐G) with better effect on ochratoxin A (OTA) was screened out in the main fermentation stage of wine. The results showed that 20‐G removed OTA through biosorption and biodegradation. Intracellular enzymes played the main role (18.44%) and yeast cell walls adsorbed a small amount of OTA (8.44%). Furthermore, the identification of proteins in 20‐G revealed that the decrease in OTA content was mainly a result of the action of peroxidase, and validation tests were carried out. By analyzing the degradation products of OTA, OTα and phenylalanine with lower toxicity were obtained. Animal experiments showed that the intervention of yeast 20‐G reduced the damage and adverse effects caused by OTA toxicity to the mice.CONCLUSIONThe present study demonstrates the mechanism of OTA removal by 20‐G and the toxicity of OTA was reduced by peroxidase in 20‐G. © 2023 Society of Chemical Industry.