Background: Apical fenestration denotes a cortical plate opening in the alveolar bone resembling a window shape and affects the apical tooth root area. The shell of green clams (Perna viridis) and golden sea cucumbers (Stichopus hermanii) possess antibacterial properties, attributed to high levels of glycosaminoglycans and calcium, aid wound healing by reducing inflammation and promoting bone regeneration. Aim: This study seeks to validate the efficacy of a gel containing a blend of green clam shell hydroxyapatite and golden sea cucumber in healing apical fenestration wounds, measured through increased TGF-β1 expression. Methods: A laboratory experimental research and clinical trial were conducted, utilizing a posttest only control group design involving 27 Wistar samples. Rodents were distributed into three categories: negative control, positive control (aloe vera gel application), and treatment (gel with green clam shells and golden sea cucumbers). Sacrifice occurred over 3, 7, and 14 days, with immunohistochemical examination for data analysis. Results: One-way ANOVA and post hoc LSD ANOVA tests revealed a significant increase in TGF-β1 expression (p<0.05) in both gingival soft tissue lesions and alveolar hard tissue defects within the treatment group. The gel effectively facilitated tissue re epithelialization and bone remodeling in healing apical fenestration wounds. Conclusion: The application of a gel containing a combination of green clam shell and golden sea cucumber proved effective in healing apical fenestration wounds in Rattus norvegicus (Wistar rat) teeth, as evidenced by the increase in TGF-β1 expression.