Spherical hydrogels (‘micro beads’) made from alginate has been explored and used for biomedical application, delivery of biomolecule and cell transplantation, although restricted mechanical strength and short-term structural cohesion. In this study, controlling mechanical properties and maintaining the long-term structural integrity of spherical hydrogels could be achieved by creating interpenetrating networks (IPN) of alginate and aqueous-soluble cellulose with divalent and trivalent ions. By using various the aqueous-soluble cellulose, with varying concentration of cellulose or types of ions, the moduli of the resulting hydrogels could be controlled in a wide range with a simple yet highly efficient method of engineering alginate beads. The aqueous-soluble cellulose is found to undergo crosslinking reaction with trivalent ions more favorably than divalent ions, processing a dual sequential ionic crosslinking scheme to create IPN of alginate and cellulose with divalent and trivalent ions, respectively. Especially, the aqueous-soluble anionic cellulose, containing either carboxylate or sulfonate, is easier to control mechanical properties than other types of celluloses. Furthermore, the IPN alginate-cellulose beads demonstrate enhanced resistance to harsh chemical environment as compared to alginate beads and suitability for biomedical applications by encapsulating microbial species and therapeutic agents for controlled release.