Periodontal Disease (PD) is one of the most common inflammatory oral diseases, affecting approximately 47% of adults aged 30 years or older in the United States. If not treated properly, PD leads to degradation of periodontal tissues, causing tooth movement, and eventually tooth loss. Conventional clinical therapy for PD aims at eliminating infectious sources and reducing inflammation to arrest disease progression, which cannot achieve the regeneration of lost periodontal tissues. Over the past two decades, various regenerative periodontal therapies, such as Guided Tissue Regeneration (GTR), enamel matrix derivative, bone grafts, growth factor delivery, and the combination of cells and growth factors with matrix-based scaffolds, have been developed to target the restoration of lost tooth-supporting tissues, including the periodontal ligament, alveolar bone, and cementum. This review discusses recent progress in periodontal regeneration using tissue-engineering and regenerative medicine approaches. Specifically, the focus is on the advances in biomaterials and controlled drug delivery for periodontal regeneration in recent years. Special attention is given to the development of advanced bio-inspired scaffolding biomaterials and temporospatial control of multi-drug delivery for the regeneration of the cementum-periodontal ligament-alveolar bone complex. Challenges and future perspectives are presented to provide inspiration for the design and development of innovative biomaterials and delivery systems for new regenerative periodontal therapy.