Over the past few decades, there has been significant progress in the field of biomaterials, specifically in addressing the challenges associated with tissue regeneration. By selecting the appropriate biomaterials and fabrication techniques, one can achieve tissue-specific architectures and structural properties for scaffolds. These scaffolds have also been modified with site-specific functionalities to facilitate optimal tissue regeneration. Despite these advancements, challenges like large-sized defects and infection-prone implant sites hinder the success of these scaffolds. To address these challenges, a highly porous poly (ɛ-caprolactone) (PCL) scaffold was developed utilizing high-internal-phase emulsion (HIPE, dispersed phase volume >74%) templating, which was further functionalized to impart antimicrobial properties. A single-step methodology was employed to create nanocomposite scaffolds made of crosslinked PCL. This was achieved by the polymerization of Pickering HIPEs of ɛ-caprolactone (CL) that were stabilized using hydrophobic silica nanoparticles (mSiNPs) at low concentrations. The developed scaffolds demonstrated cyclic compressional stability for multiple cycles. Further, the PCL nanocomposite scaffolds were functionalized using an antimicrobial therapeutic agent that could effectively prohibit the growth and formation of biofilm in the case of both S. aureus and E. coli. The developed nanocomposite scaffolds had no adverse effect on MG-63 cells, allowing their growth and surface adherence. The developed antimicrobial scaffolds of PCL demonstrated promising capability to not only allow regeneration at large defect sites but also avoidpossible implant-site infections.