Oxidative stress plays a crucial role in the development of various diseases, including diabetes, cardiovascular diseases, cancer, and rheumatic disorders. It disrupts the redox balance and initiates a series of pathological changes. As two-dimensional inorganic solids with an open structure and anion-exchange properties, layered double hydroxides (LDHs) offer significant advantages in the biomedical field, such as drug carriers, antioxidant catalysts. This article outlines application of LDHs in the treatment of cancer, rheumatic diseases, bone disorders, diabetes, Alzheimer's disease, and other conditions. More importantly, this paper elaborates on the challenges faced by the application of LDHs, including the biological activity to be explored, the performance to be optimized, and their in vivo functions and molecular mechanisms to be clarified. The solution strategies have also been discussed, which pointed out the direction for promoting the clinical transformation and application of LDHs in the future.