The sustained and controlled delivery of antimicrobial drugs has been largely studied using nanomaterials, like metal organic frameworks (MOFs), and various polymers. However, not much attention has been given to combining MOFs and biodegradable polymers towards the potentially more sustained release of active pharmaceutical ingredients. Herein, we report a comparative study of two widely used antimicrobial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated into biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) composites. Cephalexin and metronidazole were separately loaded into MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL composites. The pristine MOF-5 and the loaded MOFs were thoroughly characterised using Fourier-transformed infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Ultraviolet-visible (UV-Vis) spectroscopy studies were carried out to assess the release of the drugs in PBS for up to 72 h, showing a cumulative release of 24.95 wt% and 27.84 wt% for cephalexin and metronidazole, respectively. The antibacterial properties of the pristine MOF, pure drugs, drug-loaded MOFs and the loaded composites were assessed against Gram-positive and Gram-negative bacterial strains, Staphylococcus aureus or Staphylococcus epidermidis and Escherichia coli or Acinetobacter baumanii, respectively. A cephalexin-loaded MOF-5 composite of PCL (PCL-ceph@MOF-5) showed the best efficiency for the controlled release of drugs to inhibit the growth of the bacteria compared to the other composites. This study demonstrates that the combination of MOFs with biodegradable polymers can provide an efficient platform for the sustained release of antimicrobial drugs and can be a promising tool to manage antimicrobial resistance (AMR).