The present study was aimed to fabricate bergenin polymeric nanoparticles based hydrogel and to evaluate its therapeutic effectiveness against infected wounds. Polymeric nanoparticles were prepared through a slightly modified ionic gelation method. Blank nanoparticles were optimized using Design Expert software whereas bergenin loaded NPs (BG-NPs) were optimized by hit & trial method. Characterization of optimized bergenin loaded NPs was done through zeta sizer, FTIR and DSC. The optimized NPs had a particle size of approximately 254 nm, PDI 0.3 and zeta potential of +26 mV with an encapsulation efficiency of approximately 83%. These NPs were loaded into a secondary carrier i.e., Carbopol-934 hydrogel and then were physicochemically characterized. In vitro drug release study was carried out at two different pH values i.e., pH 5.5 and pH 7.4 and results showed a sustained release. Korsmeyer Peppas was the best fit kinetic model having highest R2 value 0.9864 and 0.9934 in case of nanodispersion and polymeric nanoparticles based hydrogel respectively. Ex vivo skin permeation and retention study showed a little permeation of drug through the skin and confirmed enhanced retention of drug within the skin layers. Antimicrobial assays showed a significant antimicrobial activity of nanoparticles against resistant and non-resistant strains as compared to the free drug. In vivo study was carried out by inducing infected wounds in male mice. Effect of different formulations in treating infected wound was examined by measuring wound size, bacterial load and histopathological evaluation. BG-NPs based hydrogel showed maximum efficacy as compared to other formulations. In a nutshell, it can be concluded that BG-NPs based hydrogel could be a reliable choice for treatment of wound infections.