One of the major health problems linked to methicillin-resistant Staphylococcus aureus (MRSA) is severe diabetic foot ulcers (DFU), which are associated with hospital-acquired infections, lower limb amputations and emerging resistance to the current antibiotics. As an alternative, this work aims to develop a biodegradable and biocompatible material with antimicrobial capacity to prevent DFU. This was achieved by producing active polymeric films with metallic nanoparticles dispersed through a polycaprolactone (PCL) dressing. First, the antimicrobial activity of copper oxide nanoparticles (CuONPs) was tested by the microdilution method, selecting the lowest concentration that has an inhibitory effect on MRSA. Then, active PCL films were prepared and characterized in terms of their physicochemical properties, antimicrobial performance, cytotoxicity, genotoxicity and hemocompatibility. Active films had chemical and thermal properties like the ones without the antimicrobial agents, which was confirmed through FTIR, Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) analysis. In relation to antimicrobial activity, active PCL films inhibited MRSA growth when treated with CuONPs at a concentration of 0.07% (w/w). After exposure to the active film extracts, human foreskin fibroblast cells (ATCC® SCRC1041™) (HFF-1) exhibited a cell viability average above 80% for all treatments and no DNA damage was found. Finally, PCL films with 0.07% (w/w) CuONPs proved to be hemocompatible, and none of the films evaluated had red blood cell breakage greater than 5%, being within the acceptable limits established by the International Organization for Standardization ISO 10993-4:2002.