Background: Heliotropium indicum and Nephrolepis biserrata are common medicinal plants used in folk medicine for treating many diseases, including wounds in most African countries such as Ghana. Previous separate preliminary studies on these two herbs have shown that they have wound-healing abilities. However, their combined effects concerning wound healing remain unknown. Many studies also have identified diverse phytocompounds in the leaves of these two medicinal plants. Objective: The present study describes the development of a polyherbal wound-healing formulation from leaves of H. indicum and N. biserrata and further assessed their wound-healing effects using both in vivo and in vitro wound healing models. Materials and methods: After the herbs leaf collection and confirmation, ethanol was used to extract phytocompounds from their dried leaves and subjected to phytochemical screening using standard methods. Subsequently, the antioxidant and free radical scavenging properties of the crude extracts were assessed. The weight: weight proportions were used to prepare the polyherbal formula and were tested using an excision wound model. Wound contraction and wounding days were used as endpoints to assess the degree of wound-healing effects. Results: Extracts of N. biserrate and H. indicum exhibited antioxidant activity with a half-maximal inhibitory concentration (IC50) value of 324.1 and 301.1 μg/mL in the 2,2-diphenyl-1-picrylhydrazyl radical scavenging method, 745.6 and 350.1 μg/mL in the nitric oxide synthase assay, and 806.4 and 180.5 μg/mL in the ferric reducing assay, respectively. The total phenolic content in N. biserrata extract was 52.271 mg gallic acid equivalent per gram of dry extract, significantly higher than 32.170 recorded in H. indicum extract. Similarly, N. biserrate extract exhibited higher total flavonoid content of 594.537 compared with 357.471 for H. indicum extract. None of the formulations gave 100% complete wound healing on the 18th day of treatment. However, the monotherapy formulations performed better than the polyherbal formulations. The 10% dosage formulation of H. indicum and the 20% dosage of 1:2 H. indicum and N. biserrata formulation recorded the highest wound healing activity of 97.4 and 93.8% among the polyherbal treatments.