The synthesis of highly antimicrobial nanocrystalline zinc oxide and its covalent modifications are presented. In order to achieve further improvement of antimicrobial activity, the surface of ZnO was effectively modified with selected silanes comprising amino- and ionic liquid-functionalities. We demonstrate for the first time ionic liquid surface immobilization on ZnO and the application of this hybrid material for antimicrobial purposes. Different microscopic and spectroscopic techniques as well as size, surface and elemental composition analyses were employed to prove these modifications. Characterization revealed that surface and antimicrobial properties strongly depend on the modification employed. Most of the amino- and ionic liquid-functionalised nanocrystalline ZnO exhibited improved antimicrobial activity compared to commercially available silane-containing antimicrobial agents attached to nanocrystalline ZnO. Bacterial growth reduction was assessed by following the optical density of bacterial growth with different concentrations of the novel antimicrobial nanomaterials. Complete bacterial inactivation was achieved for specific amino- and ionic liquid-modifications at 0.125 g L-1, revealing the synergistic effect of ZnO and its modifications, exhibiting up to 2-fold improvement compared to unmodified ZnO.