To reduce costs and environmental pollution, the alginate derivatives (Ugi-Alg) that can be applied in the field of pharmaceutical formulations were synthesized by the Ugi four-component condensation reaction using the p-tolylsulfonylmethyl isocyanide to replace cyclohexyl isonitrile and n-propionaldehyde to re-place formaldehyde, based on previous explorations of Ugi reaction for the modification of alginate. The molecular structure of Ugi-Alg were characterized by means of FT-IR and 1H NMR, and their properties were determined by TGA, XRD, fluorescence spectrum (FM), surface tension (SFT), TEM, laser particle size and zeta potential analyzers. Experimental results showed that Ugi-Alg-1 and Ugi-Alg-2 were success-fully prepared by Ugi reaction. The grafting of hydrophobic side groups broke the intramolecular hydrogen bonds of the raw SA, changing its microcrystalline structure, decreasing thermal stability, and enhancing the flexibility of the molecular chain. Moreover, the molecular chains of Ugi-Alg-1 and Ugi-Alg-2 could curl freely through hydrophobic association to form the micellar aggregates with the hydrodynamic parti-cle diameters (dH) of 659.4 nm and 534.6 nm, and Zeta potentials of -54.6 mV and-60.8 mV, respectively。These results indicated that both Ugi-Alg-1 and Ugi-Alg-2 has good colloidal interfacial activity. In addi-tion, the hydrophobic lumen of Ugi-Alg-1 and Ugi-Alg-2 can effectively solubilize the hydrophobic ibu-profen, retard the diffusion of the drug, and slow down the drug release rate. The release process of ibu-profen from Ugi-Alg drug-loaded microcapsules conformed to the Non-Fickian diffusion mechanism, in-dicating that the swelling and degradation of Ugi-Alg microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen.