Peperomia pellucida, a tropical plant belonging to the Piperaceae family, has long been recognized for its potential medicinal properties, including anti-inflammatory, analgesic, and antimicrobial effects. This study investigates the efficacy of Peperomia pellucida nanoemulsion (PPNE) as a novel therapeutic approach for improving burn wound healing in Wistar rats. The nanoemulsion was formulated using the high-energy ultrasonication method, optimized for droplet size, polydispersity index, and stability. A 30 % burn wound was induced on the dorsum of 60 Wistar rats, which were then divided into three groups: control (untreated), silver sulfadiazine (SSD) treated, and PPNE treated. Inflammatory cytokine levels (TNF-α, IL-6, and IL-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results showed that PPNE treatment significantly accelerated wound closure rates compared to both control and SSD-treated groups, with complete wound closure achieved by day 10 in the PPNE-treated group. Histopathological examination revealed improved re-epithelialization, granulation tissue formation, and collagen deposition in the PPNE group compared to the control and SSD groups. Additionally, PPNE treatment significantly reduced inflammatory cytokine levels and enhanced antioxidant enzyme activities, suggesting a reduction in inflammation and oxidative stress in the treated wounds. In conclusion, this study demonstrates the potential of P. pellucida nanoemulsion as a promising and effective therapeutic approach for improving burn wound healing. The observed enhanced wound healing properties may be attributed to the combined anti-inflammatory, antioxidant, and antimicrobial effects of the PPNE, warranting further investigation and potential clinical application.