Periodontal disease, as a prevalent public health problem, could leads to bone resorption and ultimate tooth loss. Due to the nature of interfacial hard to soft tissue structure in periodontal complex, its wound healing is more complicated than normal oral mucosa after surgical procedures. To improve the success rate of surgical regenerative therapies in periodontal tissue, having insight to the natural tissue dissimilarities and biomechanical concepts in periodontium is crucial. Optimal periodontal regeneration contains restoration of the all three components of periodontal ligament, cementum and alveolar bone. In recent decades, many researchers have developed and characterized several strategies according to interfacial tissue engineering for periodontal regeneration. In the current review, the bio-clinical principles and current strategies for periodontal regeneration and future perspective are discussed.