Effective drug delivery to specific cellular organelles presents a promising avenue for enhancing therapeutic outcomes and minimizing off-target effects. This chapter explores the utilization of natural compounds as key players in targeted drug delivery to cellular organelles. Beginning with an introduction to the significance of organelle-specific drug delivery, the chapter outlines the roles of crucial cellular organelles, including the nucleus, mitochondria, lysosome, and endoplasmic reticulum (ER). The second section provides an overview of natural compounds, emphasizing their advantages in drug delivery. Subsequently, the chapter delves into specific examples of natural compounds known for their efficacy in targeting cellular organelles. Strategies for achieving targeted drug delivery, such as passive and active targeting using liposomes, nanoparticles, ligands, and peptides, are thoroughly examined. A significant portion of the chapter is dedicated to detailing the application of natural compounds in the nucleus, mitochondria, lysosome, and ER-targeted drug delivery systems. Challenges in the field and current trends are discussed, providing insights into the future of natural compound-based drug delivery. In conclusion, this chapter underscores the potential of natural compounds as versatile tools in the pursuit of precise and efficient drug delivery to cellular organelles, offering a glimpse into the future landscape of pharmaceutical research and development.