Abstract <p>Wound healing constitutes a multifaceted and dynamic biological phenomenon that encompasses a variety of cellular and molecular mechanisms, including but not limited to inflammation, fibroblast proliferation, extracellular matrix (ECM) remodeling, and re-epithelialization. Growth factors, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and epidermal growth factor (EGF), assume pivotal roles in the orchestration of these processes. Recently, herbal bioactives have garnered considerable attention for their potential to modulate these growth factor signaling pathways, thereby accelerating tissue repair and enhancing wound tensile strength. A diverse array of phytochemicals, encompassing curcumin, quercetin, resveratrol, asiaticoside, aloe vera polysaccharides, and ginsenosides, exhibit notable anti-inflammatory, antioxidant, pro-angiogenic, and collagen-stimulating effects, thus facilitating the wound healing process. This review meticulously examines the role of herbal bioactives in regulating fibroblast proliferation, promoting angiogenesis, and aiding in ECM remodeling, which collectively contribute to effective wound closure and the enhancement of tissue integrity. Despite the encouraging preclinical and clinical evidence, obstacles such as standardization, bioavailability, and regulatory approval pose significant challenges to the widespread clinical application of these agents. Future investigations should prioritize the development of advanced drug delivery systems, including nanotechnology and bioengineered scaffolds, to optimize the therapeutic efficacy of herbal bioactives in the context of wound healing.</p> Lay Summary <p>To complete this review, the authors have searched many published papers in Web of Science, Scopus, PubMed, PubMed Prime, Cochrane Library, ScienceDirect, and Google Scholar as web resources. The present review comprehensively underscores the therapeutic relevance of several indigenous herbal bioactives in promoting wound healing, highlighting their multifaceted pharmacological actions rooted in traditional medicine yet supported by modern scientific validation. Herbal bioactives derived from plants such as <i>Curcuma longa</i> (turmeric), <i>Azadirachta indica</i> (neem), and <i>Centella asiatica</i> (gotu kola) have shown potent wound healing efficacy owing to their intrinsic anti-inflammatory, antioxidant, antimicrobial, and proliferative properties. Curcumin, the principal active compound in <i>Curcuma longa</i>, enhances collagen synthesis, modulates oxidative stress, and promotes re-epithelialization by influencing TGF-β and VEGF signaling pathways. Neem constituents like nimbidin and azadirachtin facilitate wound sterilization through antimicrobial activity while simultaneously suppressing inflammatory cytokines such as TNF-α and IL-6, thereby creating a conducive environment for tissue repair. Similarly, triterpenoids such as asiaticoside from <i>Centella asiatica</i> stimulate fibroblast proliferation, neovascularization, and extracellular matrix (ECM) remodeling, vital for granulation tissue formation and wound closure. These indigenous bioactives not only match but often synergize with standard therapies, providing enhanced efficacy with a lower risk of adverse effects. Their affordability, biocompatibility, and wide availability make them particularly valuable in low-resource healthcare settings. This review thus consolidates critical insights into the regenerative capacity of key herbal compounds and emphasizes the necessity for further mechanistic studies and clinical trials to facilitate their integration into evidence-based wound management strategies.</p> Graphical Abstract <p></p>