With the rapid development of nanotechnology, layered double hydroxides (LDHs) have attracted considerable attention in the biomedical field due to their highly tunable composition and structure, superior biocompatibility, multifunctional bioactivity, and exceptional drug delivery performance. However, a focused and comprehensive review addressing the role of LDHs specifically in tissue regeneration has been lacking. This review aims to fill that gap by providing a systematic and in-depth overview of recent advances in the application of LDHs across various regenerative domains, including bone repair, cartilage reconstruction, angiogenesis, wound healing, and nerve regeneration. Beyond presenting emerging applications, the review places particular emphasis on elucidating the underlying mechanisms through which LDHs exert their therapeutic effects. Although LDHs demonstrate considerable promise in regenerative medicine, their clinical translation remains in its infancy. To address this, we not only provided our insights into the personalized problems that arise in the application of various tissues, but also focused on discussing and prospecting the common challenges in the clinical translation of LDHs. These challenges include optimizing synthesis techniques, enhancing biosafety and stability, improving drug-loading efficiency, designing multifunctional composite materials, and establishing pathways that facilitate the transition from laboratory research to clinical practice.