A series of antimicrobial PCL/PVC/OMMTs nanobioblends films are successfully prepared via melt blending process of the poly (ϵ‐caprolactone) (PCL), poly (vinyl chloride) (PVC), and three different clay types namely Cloisite 30B (C30B), trimethylhexadecyl ammonium (OMMT1), and cetylpyridinium chloride monohydrate (OMMT2) modified montmorillonite. All the PCL/PVC/OMMTs nanocomposites display mixed intercalated/partially exfoliated structures as attested by X‐Ray Diffraction and Transmission Electron Microscopy. Glass transition, fusion and cristallization of these nanomaterials are studied using differential scanning calorimetry (DSC). The organoclay effect on the mechanical, barrier and antimicrobial properties is investigated. The results confirm that the insertion of 3 wt% of OMMT (whatever its intercalant agent nature) into the PCL/PVC matrix leads to (1) a remarkable improvement in barrier properties, (2) an interesting enhancement in mechanical properties, and (3) a strong antimicrobial activity against Staphylococcus aureus (Gram‐positive) and Escherichia coli (Gram‐negative).