**Background:** Wound healing is a complex, multistep process involving hemostasis, inflammation, proliferation, and remodeling. Acute wounds normally heal within 2–3 weeks, but factors such as diabetes, infection, or chronic inflammation can lead to non-healing chronic wounds, which cause pain, depression, and risk of amputation. Traditional medicine has long used medicinal plants for wound care, and recent scientific research aims to provide evidence for their efficacy. This narrative review focuses on in vivo studies from the last 5 years (2018–2022) that investigated the wound-healing effects of botanical extracts and pure natural substances in animal models (mice, rats, rabbits), including excision, incision, and burn wounds with or without infection.
**Methods:** The authors conducted a literature search using ScienceDirect, Web of Science, PubMed, SciFinder-n, and Scopus with keywords including “natural products,” “wound healing,” “animal models,” “burns,” “plants,” “wound dressings,” and “inflammation.” Out of 2194 research items examined, 190 fell within the scope of the review and formed the baseline for the survey. The review included preclinical in vivo studies of plant extracts and pure natural substances, focusing on their effects on wound contraction, epithelialization, collagen formation, tensile strength, and modulation of inflammatory and oxidative stress markers.
**Key Results:** The review presents data from 37 botanical extracts (Table 1) and 34 pure natural substances (Table 2). Notable findings include:
- *Aloe megalacantha* leaf latex (5% and 10% w/w ointment) significantly increased wound contraction, epithelial cell proliferation, and tensile strength in Swiss albino mice and Sprague Dawley rats.
- *Phyllanthus muellerianus* aqueous extract (0.25–1% w/w) and its pure compound geraniin (0.1–0.4% w/w) elevated fibroblast activity, collagen content, and TGF-β1 levels in male Sprague–Dawley rats.
- Biofunctionalized silver nanoparticles from clove extract (5% cream) showed notable wound-repairing effects in albino rats.
- *Nigella sativa* oil loaded into polyurethane nanofibrous mats significantly provoked wound healing in female Sprague Dawley rats.
- Quercetin, studied in multiple formulations (0.03–0.3% in gels, nanoparticles, nanofibers), accelerated wound closure, reduced immune cell infiltration, and modulated cytokines and growth factors in both diabetic and nondiabetic rat models. For example, 0.3% quercetin in DMSO improved antioxidant parameters and growth factor modulation in Wistar rats.
- Thymoquinone (0.5% w/w nano-emulgel) showed faster and better wound healing compared to ordinary hydrogel in Wistar rats.
- Curcumin conjugated with hyaluronic acid enhanced wound healing in diabetic Swiss male albino mice compared to free curcumin or hyaluronic acid alone.
- Cinnamaldehyde (25–100 mg/kg intraperitoneal) induced angiogenesis and increased wound repair rate in diabetic and normal mice.
- Luteolin (100 mg/kg intraperitoneal or 0.5–1% ointment) improved wound restoration by reducing inflammation and oxidative stress in diabetic and nondiabetic rats.
- Vicenin-2 hydrocolloid films efficiently enhanced wound repair in hyperglycemic Sprague Dawley rats.
- Kaempferol (1% w/w ointment) was effective in both diabetic and nondiabetic wounds in Wistar rats.
- Glycyrrhizin micelle encapsulating genistein (DG-Gen 1:15) significantly prompted corneal re-epithelialization and nerve regeneration in diabetic C57BL/6J mice.
- Micro-channeled alkylated chitosan sponge (MACS) showed high pro-coagulant and hemostatic effects in lethal conditions in rats and pigs.
- Green tea catechin EGCG-grafted silk fibroin hydrogels (SF-T70/SF-EGCG30) exerted remarkable wound healing over commercial DuoDERM® gel in Sprague Dawley rats.
**Clinical Implications:** The review provides strong preclinical evidence that natural products can effectively promote wound healing through multiple mechanisms, including antioxidant, anti-inflammatory, and antimicrobial activities. Incorporating these bioactive compounds into modern wound dressings (nanofibers, hydrogels, films, scaffolds) addresses limitations such as poor solubility and controlled release, and enhances healing outcomes, especially in diabetic and infected wounds. The authors emphasize that these findings support the potential of natural products as safe, effective, and low-side-effect alternatives for wound management. However, they stress the need for multidisciplinary efforts to confirm safety, evaluate adverse effects, and conduct double-blind controlled clinical trials. Good production standards and regulatory regulations are essential to integrate phytotherapy into mainstream wound care.