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Soft tissue reconstruction of oral cavity defects, such as glossectomy defects secondary to malignancy, pose a challenge for head and neck, oral, and maxillofacial surgeons. Reconstruction options for mucosal defects include primary closure, healing by secondary intention, full mucosal and split-thickness skin grafts, pedicled flaps, and microvascular free flaps. Biological grafts have become an integral part of the modern reconstructive ladder and are widely used for the regeneration of various soft tissue defects, including oral defects. This case series describes our initial experience using ovine forestomach matrix grafts in tongue and oral cavity reconstruction. Oral reconstruction using ovine forestomach matrix grafts was undertaken on three patients post wide excision and resulted in good functional and cosmetic outcomes. The rate of tissue formation provided by the graft and the grafts’ relative resistance to the hostile environment of the oral cavity support further clinical research to validate the use of these devices in oral reconstruction.