Advanced lipoxidation end products (ALEs) are formed by modifying proteins with lipid oxidation products. The health effects of ALEs formed in vivo have been extensively studied. However, the digestibility, safety, and health risk of ALEs in heat-processed foods remain unclear. This investigation was performed to determine the structure, digestibility, and effect on the mice liver of dietary ALEs. The results showed that malondialdehyde (MDA) was able to alter the structure of myofibrillar proteins (MPs) to form linear, loop, and cross-linked types of Schiff bases and dihydropyridine derivatives under simulated heat processing, leading to the intra-and intermolecular aggregation of MPs and, thus, reducing the digestibility of MPs. In addition, dietary ALE intake resulted in abnormal liver function and lipid accumulation in mice. The core reason for these adverse effects was the destructive effect of ALEs on the intestinal barrier. Because the damage to the intestinal barrier leads to an increase in lipopolysaccharide levels in the liver, it induces liver damage by modulating hepatic lipid metabolism.