Background: Previous in vitro studies showed that sesame oil stimulates fibroblast production in wounds. Many studies investigated the therapeutic wound healing properties of natural products. The current study aimed at evaluating the effect of the combination of sesame oil and Cucurbita as a novel herbal mixture on healing the local wounds caused by the third-degree burn. Methods: The current experimental study was conducted on 24 adult BALB/c mice randomly divided into experimental groups. Then, all mice were sacrificed and a sample of wound bed was provided and fixed in formalin, followed by the practical histologic process. The samples were stained with the Mallory-Trichrome technique and investigated under microscopy. A Part of the sample was frozen to extract protein, perform malondialdehyde (MDA) test, and measure total antioxidant. Results: A complete tightening of the wound and less scar was observed in the macroscopic observation of burn wounds in the group treated with sesame oil and pumpkin (treatment group 5) compared with the control and other groups. In the microscopic assessments, a significant increase (P < 0.05) was observed in the total thickness of skin, and number and diameter of the hair follicles in the experimental group compared with other groups. Conclusions: The current study results showed that a combination of sesame oil and pumpkin at different concentrations accelerated the healing process of burn wounds in BALB/c mice, while using the under study materials separately had less effects on the improvement of skin wounds compared with the combination form.