Bacterial cellulose (BC) has emerged as a promising biomaterial for wound healing due to its high purity, biocompatibility, and good water-retention properties. In this study, a novel bioactive paste made by incorporating a neem-hypericum oil-in-water emulsion into fibrillated bacterial cellulose (BC-NHE), was tested for its in-vitro biocompatibility, in-vivo acute toxicity and wound healing in rat animal model. In vitro cytocompatibility studies using L929 fibroblast cells demonstrated high cell viability (>85%) across all tested concentrations, indicating low cytotoxicity. Acute toxicity assessment in Sprague-Dawley rats, conducted according to ISO 10993-11 guidelines, revealed no systemic toxicity, behavioral abnormalities and abnormal histopathological alterations in major organs. The wound healing capabilities of BC-NHE were evaluated using a full-thickness excisional wound in rat model and compared with a commercial collagen dressing. The BC-NHE-treated group exhibited significantly accelerated wound contraction (∼98% closure by day 21), enhanced re-epithelialization, increased collagen deposition, and improved tissue organization relative to both positive and negative controls. Histological analysis confirmed advanced healing with reduced inflammation and well-structured dermal regeneration. Overall, the developed BC-NHE paste demonstrates excellent biocompatibility, safety, and superior wound healing efficacy, highlighting its potential as a multifunctional biomaterial for advanced wound care applications.