Periodontal disease is an infection-driven inflammatory disease characterized by the destruction of tooth-supporting tissues. The establishment of chronic inflammation will result in progressive destruction of bone and soft tissue changes. Severe periodontitis can lead to tooth loss. The disease has complex pathogenesis with an interplay between genetic, environmental, and host factors and pathogens. Effective management consists of plaque control and non-surgical interventions, along with adjuvant strategies to control inflammation and disrupt the pathogenic subgingival biofilms. Recent studies have examined novel approaches for managing periodontal diseases such as modulating microbial signaling mechanisms, tissue engineering, and molecular targeting of host inflammatory substances. Mounting evidence suggests the need to integrate omics-based approaches with traditional therapy to address the disease. This article discusses the various evolving and future drug targets, including proteomics, gene therapeutics, vaccines, and nanotechnology in personalized periodontal medicine for the effective management of periodontal diseases.