Aim The current research aimed to evaluate the potential effect of adding platelet-rich fibrin (PRF) to the decellularized bovine pericardium (DBP) on the distal limb of donkeys' full-thickness cutaneous wounds healing (Equus asinus). Materials and Methods Healthy male donkeys (n = 12) were used in this study. Under general anesthesia, 6 cm2 full-thickness incisions were made on the middle dorsolateral surface of both forelimbs' metacarpi. The left forelimbs were control wounds, while the right wounds were treated with PRF/DBP. Control wounds were bandaged with a standard dressing after saline irrigation and were evaluated at days 4, 7, 10, 13, 16, 19, 22, 25, and 28 post-wounding. PRF/DBP-treated wounds were dressed with a combination of PRF/DBP at the first, second, and third weeks postwounding. Clinical and histopathological examinations of the wounds were performed to assess the healing process. Additionally, the immunohistochemical evaluation and gene expression profiles of myofibroblastic and angiogenic genes (transforming growth factor-beta 1, vascular endothelial growth factor-A, fibroblast growth factor 7 (FGF-7), and collagen type 3 alpha 1) were analyzed. Results PRF/DBP wounds had a significantly faster healing process (61.3 +/- 2.6 days) than control wounds (90.3 +/- 1.4 days) (p < 0.05). The immunohistochemical examination and gene expression profile revealed significant enrichment in PRF/DBP wounds compared to control wounds. Conclusion PRF/DBP dressing can be considered a natural and cost-effective biomaterial for enhancing the recovery of donkeys' distal limb injuries.