Abstract: This study aimed to compare incisional wound healing in cats and dogs after the topical application of Manuka honey and a new medical device, Dermapliq. Comparisons were made between each treatment and control, between the two treatments, and between dogs and cats. Twelve cats and twelve dogs were included in this study, and the impact of the two substances was examined through cosmetic, clinical, ultrasonographical, and histological evaluation. The use of Dermapliq in first-intention wound healing achieved a significantly better cosmetic evaluation score and better total clinical score at days 20–41, compared to the control, in both dogs and cats. The ultrasonographically estimated wound area was smaller with Dermapliq compared to the control. Wounds treated with Dermapliq showed histologically less inflammation compared to the control. The use of Manuka honey did not show a significantly better cosmetic score compared to the control. Skin thickening was significantly higher after using Manuka honey compared to the control and so was the total clinical score. However, the median wound area, as was evaluated ultrasonographically, was significantly smaller when wounds were treated with Manuka honey, the difference being more apparent in dogs. Dermapliq was proven to be a better choice in achieving favorable wound healing than Manuka honey in dogs and cats in first-intention healing. In our study, cats had a statistically better cosmetic score and less skin thickening and scar width compared to dogs. Histologically, cats showed significantly less edema, higher inflammation and angiogenesis scores, and lower fibroblast and epidermis thickening scores when compared to dogs.