Clay-based biopolymers are among the most efficient and cost-effective composite materials that find applications in a variety of biomedical applications such as drug delivery. This chapter elaborates the different physical, chemical, and structural properties of clay biopolymeric composites, which makes them most reliable to use for the applications of drug delivery. The main focus of writing this chapter is to explore the composition, structural properties, and route of action of clay-based nanomaterials, along with elaborating the mechanism of the drug delivery system. The synthesis of clay-encapsulated drug formulation and their route of administration has been investigated in this chapter. Data for the synthesis of composites and in vitro study has also been included from the existing literature.