The aim of the present study was to evaluate effects of curcumin-polyethylene glycol loaded on chitosan-gelatin nanoparticles (C-PEG-CGNPs) on burn wound healing in rat as a model study. Sixty healthy male White Wistar rats were randomized into four experimental groups of 15 animals each: Control group (Control) was treated with normal saline. Carrier group was treated with CGNPs-based ointment (0.05 mg/ml). Silver sulfadiazine group was treated with silver sulfadiazine 1% ointment. Treatment group was treated with C-PEG-CGNPs (0.05 mg/ml). Wound size was measured on 7, 14, and 21 days after surgery. The expression of p53, Bcl-2, caspase-3 were evaluated using reverse transcription-polymerase chain reaction and immunohistochemical staining. Reduction in wound area indicated that there was significant difference between Treatment group and other groups (P < .05). Quantitative histological and morphometric studies, and mean rank of the qualitative studies demonstrated that there was a significant difference between Treatment group and other groups (P < .05). Observations demonstrated C-PEG-CGNPs significantly shortened the inflammatory phase and accelerated the cellular proliferation. Accordingly, the animals in Treatment group revealed significantly (P < .05) higher fibroblast distribution/one mm2 of wound area and rapid reepithelialization. The mRNA levels of Bcl-2, p53, and caspase-3 were remarkably (P < .05) higher in Treatment group compared to control animals. The immunohistochemical analyses confirmed the reverse transcription-polymerase chain reaction findings. C-PEG-CGNPs offered potential advantages in burn wound healing acceleration and improvement.