The physiological healing process is disrupted in many cases using the current wound healing procedures, resulting in delayed wound healing. Hydrogel wound dressings provide a moist environment to enhance granulation tissue and epithelium formation in the wound area. However, exudate accumulation, bacterial proliferation, and reduced levels of growth factors are difficulties of hydrogel dressings. Here, we loaded platelet-rich fibrin-chitosan (CH-PRF) nanoparticles into the gelatin-chitosan hydrogel (Gel-CH/CH-PRF) by solvent mixing method. Our goal was to evaluate the characteristics of hydrogel dressings, sustained release of proteins from the hydrogel dressing containing PRF, and reduction in the risk of infection by the bacteria in the wound area. The Gel-CH/CH-PRF hydrogel showed excellent swelling behavior, good porosity, proper specific surface area, high absorption of wound exudates, and proper vapor permeability rate (2023 g/m .day), which provided requisite moisture without dehydration around the wound area. Thermal behavior and the protein release from the hydrogels were investigated using simultaneous thermal analysis and the Bradford test, respectively. Most importantly, an excellent ability to control the release of proteins from the hydrogel dressings was observed. The high antimicrobial activity of hydrogel was confirmed using Gram-positive and Gram-negative bacteria. Due to the presence of chitosan in the hydrogels, the lowest scavenging capacity-50 value (5.82 μgmL) and the highest DPPH radical scavenging activity (83 %) at a concentration 25 μgmL for Gel-CH/CH-PRF hydrogel were observed. Also, the hydrogels revealed excellent cell viability and proliferation. The wound healing process was studied using an in vivo model of the full-thickness wound. The wound closure was significantly higher on Gel-CH/CH-PRF hydrogel compared to the control group, indicating the highest epidermis thickness, and enhancing the formation of new granulation tissue. Our findings demonstrated that Gel-CH/CH-PRF hydrogel can provide an ideal wound dressing for accelerated wound healing.