Owing to the multiple beneficial effects presumed for guided tissue regeneration (GTR) systems in the treatment of periodontitis including; preventing connective tissue from interfering in osteogenesis, creating a space for the growth of cells, enhancing the healing process of degenerated periodontal ligament and tissues, preventing inflammation, and bacterial infection, these systems have been the center of attention recently. Along with all these advantages, GTR systems are capable of acting as drug carriers for the targeted and prolonged delivery of drugs into the oral cavity with fewer side effects. The reduced frequency of administration compared to systemic dosage forms means higher patient compliance and satisfaction. Throughout the last decades, scientists have attempted to design and develop such systems in multiple studies for dual aims of concurrent tissue regeneration and delivery of various therapeutic agents including antibiotics, anti-inflammatories, topical antiseptics, growth factors and so forth. Despite the significant positive results achieved by drug-loaded GTR systems, there is no commercially manufactured and approved GTR system for drug delivery to date. It is therefore essential to have a suitable perspective of the world's current position/perspective in the development of these systems to take the process to the next level. The present manuscript for the first time reviews studies on GTRs and discusses their most important findings including the main matrix component, method of fabrication, use solvent systems and release patterns to name a few in relation to the aforementioned aim.