The development of multifunctional encapsulation biomaterials could help the translation of cell‐based therapies into standard medical care. One of the major hurdles in the field of encapsulated cell transplantation is the current lack of materials presenting optimal properties, including long term stability, mechanical durability and non‐immunogenic character. Modification of sodium alginate (Na‐alg) with polyethylene glycol (PEG) derivatives, without restricting its gelling abilities, appeared as an efficient strategy to produce dual ionic‐covalent spherical hydrogels with enhanced mechanical performance as well as drug‐eluting microspheres (MS) for the mitigation of inflammatory response after transplantation. In this study, the combination of PEGylated alginates equipped with cross‐reactive functionalities and the anti‐inflammatory drug ketoprofen (KET) resulted in the assembly of multifunctional (MF) hybrid MS, merging the advantages of ionic‐covalent hydrogels with the ability for controlled drug delivery. Physical characterization confirmed their improved mechanical resistance, their higher shape recovery performance and increased stability toward non‐gelling ions, as compared to pure Ca‐alg hydrogels. In vitro release kinetics revealed the controlled and sustained delivery of KET for over two weeks.