Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due to the improved biopharmaceutical and pharmacokinetic properties and targeted and controlled drug release, nano-based drug delivery systems have emerged as a promising strategy for the treatment of periodontal defects, allowing for increased efficacy and safety in controlling local inflammation, establishing a regenerative microenvironment, and regaining bone and attachments. This review provides an overview of nano-based drug delivery systems and illustrates their practical applications, future prospects, and limitations in the field of periodontal tissue regeneration.