This study involves the design, development and evaluation of a new multifunctional prosthetic mesh for treatment of abdominal wall defects without complications. The developed prosthetic mesh is a hybrid platform of both synthetic and natural materials with its backbone consisting of a synthetic commercial polyester fabric (CPF) to provide the required mechanical integrity. The CPF mesh was coated by a natural biodegradable, biocompatible and antimicrobial layer of chitosan (CS) incorporating phenytoin (PH)-loaded pluronic nanomicelles for healing promotion, and ciprofloxacin (CPX)-alginate polyelectrolyte complex-based microparticles as antibacterial agent. The prosthetic mesh was optimized and evaluated in-vitro and in-vivo. The optimum PH-loaded micelles had particle size of 95.42 nm, polydispersity index of 0.41, zeta potential of -18 and entrapment efficiency of 89.4%, while the optimum CPX microcomplexes had particle size of 1292.0 nm, polydispersity index of 0.8, zeta potential of -20.1, complexation efficiency of 81.1%, and minimum inhibitory concentration of 0.25 μg/ml and 0.125 μg/ml against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. In-vivo study on abdominal wall defect dog model was conducted, followed by implantation of the proposed prosthetic meshes. The developed mesh depicted an efficient healing with excellent biocompatibility, and could be an ideal and feasible alternative prosthesis with many advantages such as low cost, inertness, mechanical stability, pliability, low infection rate, limited modification by body tissues, sterilizability, non-carcinogenicity, limited inflammatory reaction, hypoallergenic as well as minimal complications.