Pulpo-periodontal lesion is one of the most complicated condition to be treated as it needs more accurate diagnostic skills and precise treatment plans. The major challenge in the treatment of the pulpo-periodontal lesion is to treat the endodontic infection along with the regeneration of the lost periodontal structures associated with the lesion. The prognosis of the tooth depends upon the extension of the periodontal structure loss around the tooth. Root canal therapy and guided tissue regeneration technique with bone grafts and collagen membranes serve as a best mode of treatment for pulpo -periodontal lesions. There are many systematic approaches and materials that are available for the treatment of the Endo-Perio lesion. Membranes used in Guided Tissue Regeneration procedures should enhance the growth of lost periodontal structures and also adapt to the surface contours of the bone and root surfaces. Autogenous grafts have proven to be the golden standard in the field of regenerative medicine. Amniotic membrane is one such gift from mother nature which has a reservoir of Mesenchymal Stem Cells which enhances the healing process along with various other properties such as Anti-Microbial (broad-spectrum against bacteria, fungi, protozoa, and viruses), Reduction of pain, Anti-Scarring and Anti-inflammatory effects, Tissue repair with enhanced bone remodeling, osteogenesis, and chondrogenesis, Accelerating fibrogenesis and angiogenesis, Increased extracellular matrix deposition. This case series presents the successful management of teeth affected by Pulpo-Periodontal lesion with Guarded Prognosis using Amniotic Membrane as a Guided Tissue Regeneration Membrane.