Purpose <p>Cyclodextrins (CDs) are cyclic oligosaccharides widely employed in pharmaceutical formulations due to their unique ability to form inclusion complexes with a broad range of drugs thus improving their solubility and bioavailability. In recent years, chemical modification of CDs has emerged as a powerful strategy to enhance their drug delivery capabilities. This review provides a focused overview of chemically modified CDs developed in the last 15 years (2010–2025) with the aim of improving solubility, drug encapsulation efficiency, and delivery.</p> Methods <p>Particular attention is given to the synthetic strategies employed to obtain functionalized CDs capable of providing enhanced biopharmaceutical properties such as improved drug solubility, receptor binding features, drug retention and permeation on absorption sites.</p> Conclusions <p>Tailored chemical modifications have been reported to improve the pharmacokinetics, bioavailability, and controlled release of encapsulated drugs, thereby helping to address some limitations of native CDs and potentially supporting the development of advanced drug delivery systems with improved selectivity and reduced side effects. Progress in this field underscores the importance of molecular design in the development of next-generation pharmaceutical excipients.</p>