Novel beta-cyclodextrin polymer (CD)-based drug delivery hydrogels were prepared by varying type and concentration of crosslinkers and optimizing the gel synthesis conditions. For comparison, dextrose gels were prepared using the same crosslinkers. The optimized gels were characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), and X-ray diffraction (XRD) as well as swelling and release studies. For drug release studies, the gels were loaded with three different model antibiotics varying in size and hydrophobicity: rifampin (RM), novobiocin (NB), and vancomycin (VM), using a common solvent method. The loading efficiency was calculated and release kinetics were determined in vitro. As expected for affinity-based mechanisms, the release of drugs, from CD-based gels, was slower than release from dextrose gels which indicated that the antibiotics all form inclusion complexes with CD. Release kinetics were also more linear in the observed time frame when using CD-based hydrogels versus dextrose hydrogels. This modification in release depended on the affinity-between CD and drug, such that larger drugs and more hydrophilic ones had their release profiles altered less than small hydrophobic ones. In conclusion, affinity-based mechanisms can be used to load antibiotics and obtain longer, more linear release profiles than purely diffusion-based mechanisms.