Abstract: In recent years, approximately 40% of globally marketed drugs are poorly water-soluble, and this proportion reaches as high as 90% in the current R&D pipeline. The low bioavailability resulting from poor solubility of hydrophobic drugs has become one of the core bottlenecks in modern drug delivery. As a widely applied biomacromolecule, alginate, a natural marine polysaccharide polymer, is characterized by abundant sources, biodegradability, good biocompatibility, and ease of chemical modification. Meanwhile, montmorillonite, owing to its large specific surface area, high cation exchange capacity, and excellent adsorption properties, occupies an important position among natural layered silicate minerals as a functional material. The drug carriers constructed by combining these two materials can not only integrate the advantages of both but also form novel delivery systems with synergistic effects. This review systematically summarizes the preparation strategies, mechanisms for regulating physicochemical properties, and research progress in hydrophobic drug delivery of alginate/organomontmorillonite composite materials. Firstly, the delivery challenges of hydrophobic drugs and the rationale for synergistic construction of the composites are analyzed. Secondly, the hydrophobic chemical modification of alginate and the organic intercalation modification of montmorillonite are respectively elaborated, with particular emphasis on the novel route of safe medical modification based on green nonionic surfactants. Subsequently, from the perspectives of major formulation types including composite hydrogels, hydrogel microspheres, Pickering emulsions, composite nanofiber dressings, and bone tissue engineering materials, the current application status and drug release kinetic profiles of the composites in the controlled release of hydrophobic drugs are systematically summarized. Finally, the core challenges facing clinical translation and future development directions in this field are further discussed. Compared with conventional carriers such as liposomes and solid dispersions, the distinctive advantages of this composite system lie in the green safety profile conferred by the natural polysaccharide/clay synergistic construction strategy, the synergistic enhancement of high drug loading and sustained release, and the flexible adaptability across multiple dosage forms, rendering it particularly suitable for long-term oral administration and wound healing applications where safety is of paramount concern.