The development of nanocomposite-based drug-delivery systems has emerged as a transformative approach for achieving controlled and sustained release profiles, particularly for the drugs with poor bioavailability and stability. Polylactic Acid (PLA) and Layered Double Hydroxides (LDHs) are two of the most promising materials in this field, each with unique benefits. This chapter explores the potential of LDH/PLA nanocomposites in controlled drug delivery for biomedical applications. LDHs, due to their distinctive layered composition and adjustable characteristics, provide a compelling framework for the encapsulation of drugs and precise release to specific targets. PLA, a polymer that is both biocompatible and biodegradable, is used as a versatile matrix to enclose these drug-laden LDHs and control their release characteristics. The chapter commences by describing the specific characteristics of LDHs and PLA, emphasizing their fundamental of drug release mechanisms, the factors influencing it, and the controlled drug release strategies of the nanocomposites. It explores several methods used for fabricating LDH/PLA nanocomposites, such as sol–gel and co-precipitation methods, the optimization of the nanocomposite formulation, and role of processing parameters that are briefly mentioned. The techniques for characterization for the nanocomposites such as morphological, thermal, surface, and rheological are explored as well. The chapter focuses on various processes that regulate the release of drugs from LDH/PLA nanocomposites. We explored factors such as LDH composition, morphology, and drug interaction. The relationship between the degradation of PLA and the kinetics of drug release is explained, highlighting the capability to develop systems that have continuous, specific, or controlled release patterns. Moreover, the chapter discusses important factors such as biocompatibility, cytotoxicity, and in vivo performance of these nanocomposites. It highlights the latest progress in the application of LDH/PLA nanocomposites for the delivery of several therapeutic agents, including anticancer drugs, antibiotics, and gene therapy vectors. The chapter concludes by outlining future possibilities and challenges linked to this promising technology, emphasizing its capacity to transform personalized medicine and tailored drug delivery systems.