Periodontal disease, root caries, maxillofacial deformity, and trauma will cause defects in periodontal supporting tissue, such as alveolar bone, gingiva, and periodontium. Low-intensity pulsed ultrasound(LIPUS) can generate hyperthermia and mechanical stimulation, which can promote the generation and differentiation of cementoblast, odontoblast, and periodontal ligament cell(PDLC). PDLC can differentiate into mesodermal lineages and subsequently generate alveolar bone, cementum, and periodontium. Alkaline phosphatase(AKP) and osteocalcin(OCN) are the advanced markers of osteogenesis and osteogenic differentiation. LIPUS-stimulated PDLC shows improved AKP activity and OCN expression. LIPUS can also decrease the root absorption during orthodontic treatment; accelerate the proliferation, differentiation, and mineralization of cementoblast, which can repair root defects; and improve the expression of connective tissue growth factor that can accelerate angiogenesis and healing of periodontal tissue. LIPUS, as a safe and non-invasive treatment, can be applied in periodontal tissue regeneration. However, further research should be conducted to determine the most suitable stimulation intensity and treatment time.