The combination of active pharmaceutical ingredients in the form of ionic liquids or organic salts (API-OSILs) with mesoporous silica nanoparticles (MSNs) as drug carriers can provide a useful tool in enhancing the capabilities of current antibiotics, especially against resistant strains of bacteria. In this publication, the preparation of a set of three nanomaterials based on the modification of a MSN surface with cholinium ([MSN-Chol][Cip]), 1-methylimidazolium ([MSN-1-MiM][Cip]) and 3-picolinium ([MSN-3-Pic][Cip]) ionic liquids coupled with anionic ciprofloxacin have been reported. All ionic liquids and functionalized nanomaterials were prepared through sustainable protocols, using microwave-assisted heating as an alternative to conventional methods. All materials were characterized through FTIR, solution 1H NMR, elemental analysis, XRD and N2 adsorption at 77 K. The prepared materials showed no in vitro cytotoxicity in fibroblasts viability assays. The minimum inhibitory concentration (MIC) for all materials was tested against Gram-negative K. pneumoniae and Gram-positive Enterococcus spp., both with resistant and sensitive strains. All sets of nanomaterials containing the anionic antibiotic outperformed free ciprofloxacin against resistant and sensitive forms of K. pneumoniae, with the prominent case of [MSN-Chol][Cip] suggesting a tenfold decrease in the MIC against sensitive strains. Against resistant K. pneumoniae, a five-fold decrease in the MIC was observed for all sets of nanomaterials compared with neutral ciprofloxacin. Against Enterococcus spp., only [MSN-1-MiM][Cip] was able to demonstrate a slight improvement over the free antibiotic.