<p>Chlorogenic acid, a naturally occurring polyphenol derivative, has excellent therapeutic properties but suffers with very low permeability. The optimized CGA nanotransfersome and nanoprotransfersome (CGATs and CGAPTs) will enhance the physicochemical properties and show improved therapeutic effects when compared with plain CGA for <i>in vitro</i> antioxidant, antibacterial, and wound healing activity by excision wound model in rats. These film hydration and phase separation coacervation methods yielded CGATs and CGAPTs which were characterized for different attributes like particle size, morphology, entrapment efficiency, zeta potential, deformability, rate of spontaneity, <i>in vitro</i> diffusion, <i>ex vivo</i> permeability, and long-term stability. CGATs and CGAPTs hydrogels were formulated with Carbopol 934 and were evaluated for pH, rheology, and skin irritation. Optimized CGATs and CGAPTs showed particle size of 584.5 ± 27 nm and 315.6 ± 13 nm with PDI values of 0.517 and 0.423 with stable zeta potential values of −28.8 ± 7.03 mV and −34.1 ± 6.6 mV, respectively. The CGATs and CGAPTs vesicles showed higher entrapment (≥99%) and excellent deformability with ≥2-fold increase in cumulative permeability with long-term stability. Lethal antibacterial effects were observed on different Gram-positive and Gram-negative strains with low minimum inhibitory concentration (MIC) values (4.58X and 16X times less). Improved DPPH radical scavenging and Fe²⁺ chelation ability were obtained with CGATs &gt; CGAPTs as compared to CGA. Remarkable reduction in wound area with higher wound contraction percentages on the 9th day was obtained with CGATs (99.43%) &gt; CGAPTs (98.45%) in comparison to marketed and CGA hydrogel (88.89%). These results show the potentiality of CGATs and CGAPTs for topical application. This is the first study of CGA in nanotransfersome and nanoprotransfersome topical delivery system.</p> Graphical Abstract <p></p>