Polyelectrolyte-multilayer microcapsules are made by layer-by-layer (LbL) assembly of oppositely charged polyelectrolytes onto sacrificial colloidal particles, followed by core removal. In this paper, contact-killing polyelectrolyte microcapsules are prepared based solely on polysaccharides. To this end, water-soluble quaternized chitosan (QCHI) with varying degrees of substitution (DS) and hyaluronic acid (HA) are assembled into thin films. The quaternary ammonium groups are selectively grafted on the primary amine group of chitosan by exploiting its reaction with glycidyltrimethylammonium chloride (GTMAC) under homogeneous aqueous acidic conditions. The morphology of the capsules is closely dependent on the DS of the quaternized chitosan derivatives, which suggests differences in their complexation with HA. The DS is also a key parameter to control the antibacterial activity of QCHI against Escherichia Coil (E. coli). Thus, capsules containing the QCHI derivative with the highest DS are shown to be the most efficient to kill E. coli while retaining their biocompatibility toward myoblast cells, which suggests their potential as drug carriers able to combat bacterial infections.