Through charge-driven interfacial complexation, we produced millimetre-sized spheroidal hydrogels (SH) with a core-shell structure allowing long term stability in aqueous media. The SH were fabricated by extruding, drop-wise, a cationic cellulose nanofibril (CCNF) dispersion into an oppositely charged polyacrylic acid (PAA) bath. The SH have a solid-like CCNF-PAA shell, acting as a semi-permeable membrane, and a liquid-like CCNF suspension in the core. Swelling behaviour of the SH was dependent on the osmotic pressure of the ageing media. Swelling could be supressed by increasing the ionic strength of the media as this enhanced interfibrillar interactions and thus strengthened the outer gel membrane. We further validated a potential application of SH as re-usable matrixes for glucose oxidase (GOx) entrapment, where the SH work as “microreactors” from which substrate and product are freely able to migrate, through the SH shell whilst avoiding enzyme leakage.