Background: Development of multidrug-resistant (MDR) organisms is becoming a critical clinical problem for the management of numerous bacterial infections. Investigating other antibacterial drugs is urgently needed that are nontoxic and effective by different mechanisms. Methods: This study was aimed to develop silver nanoparticles (AgNPs) utilizing a green synthetic approach involving highly solubilized curcumin in freeze dried nanocrystals (CrNC) as a natural flavonoid reducing agent. Results: The fabricated silver nanoparticles were typically found to be spherical in shape with particle size distribution in the range of 10–50 nm and zeta potential of -18.3 ± 2.69mV. UV-Vis spectroscopy presented a characteristic plasmon peak of silver at 410 nm. The minimal inhibitory concentrations (MICs) of the prepared AgNPs against Staphylococcus aureus ATCC® 43300™*, Escherichia coli ATCC® 8739™*, Pseudomonas aeruginosa ATCC® 27853™* and Klebsiella pneumoniae ATCC® 33495™* were 7.8, 1.9, 3.9 and 1.9 µg/ml, respectively. The in-vitro cytotoxicity on human lung fibroblast cells demonstrated that green synthesized silver nanoparticles were nontoxic at the MIC. The in-vivo study revealed that AgNPs loaded hydrogel presented an improved antibacterial efficacy and wound healing effect, with normal skin appearance when compared with silver sulfadiazine cream (Dermazin®). Conclusion: The present investigation suggests that green synthesized silver nanoparticles are going to be a promising therapeutic nontoxic antibacterial agent against MDR bacteria with improved wound healing efficacy.