Periodontal disease, characterized by inflammation and infection of the supporting structures of teeth, presents a significant challenge in dentistry and public health. Current treatment modalities, while effective to some extent, have limitations in achieving comprehensive periodontal tissue regeneration. This comprehensive review explores the potential of stem cell therapy in advancing the field of periodontal regeneration. Stem cells, including mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise due to their immunomodulatory effects, differentiation potential into periodontal tissues, and paracrine actions. Preclinical studies using various animal models have revealed encouraging outcomes, though standardization and long-term assessment remain challenges. Clinical trials and case studies demonstrate the safety and efficacy of stem cell therapy in real-world applications, especially in personalized regenerative medicine. Patient selection criteria, ethical considerations, and standardized treatment protocols are vital for successful clinical implementation. Stem cell therapy is poised to revolutionize periodontal regeneration, offering more effective, patient-tailored treatments while addressing the systemic health implications of periodontal disease. This transformative approach holds the potential to significantly impact clinical practice and improve the overall well-being of individuals affected by this prevalent oral health concern. Responsible regulatory compliance and a focus on ethical considerations will be essential as stem cell therapy evolves in periodontal regeneration.