Purpose One of the most serious and devastating complications of diabetes mellitus is diabetic ulcers. They are difficult to treat and often result in limb loss. Topical sucralfate and platelet-rich plasma have the potential to improve the healing outcomes of chronic ulcers, including diabetic ulcers. This research aims to determine the effectiveness of sucralfate and platelet-rich plasma therapy for the improvement of diabetic ulcer wound healing. Patients and Methods Ninety Wistar rats were used in this study and were classified into five groups. Four of the five groups were diabetic induced and were treated with topical sucralfate only, platelet-rich plasma only, combination of topical sucralfate and platelet-rich plasma, and diabetic control group which received standard therapy only. The non-diabetic control group did not receive any therapy. We observed macrophage amount, platelet-derived growth factor, vascular endothelial growth factor, and hypoxia-inducible factor as a biomarker. Rats were terminated after 7th and 14th days and were subjected to immunohistochemistry staining and examination. Results We found that topical sucralfate and platelet-rich plasma increase macrophage levels, vascular endothelial growth factor expression and platelet-derived growth factor expression in diabetic wound cells. We also found a reduction in hypoxia inducible factor-1α expression. Combination of topical sucralfate and platelet-rich plasma for 14 days gave the most significant improvement in terms of wound healing compared to topical sucralfate or platelet-rich plasma alone. Conclusion The combination of topical sucralfate and platelet-rich plasma therapy results in the best improvement in diabetic ulcer wound healing compared to sucralfate or platelet-rich plasma monotherapy or conventional wound healing therapy.