Porphyromonas gingivalis is the conductor of the orchestration of periodontium inflammation. Considering that a wide range of antibiotics have lost their activities in the last century, this study aimed to introduce novel and broad-spectrum drug targets against this pathogen. For this purpose, the core proteins of 17 P. gingivalis strains were obtained. Out of 1418 core proteins, 166 cytoplasmic, essential factors with no sequence similarity to host were selected. Fifty-two P. gingivalis metabolome-specific proteins were detected and then 31 novel drug targets were identified using the DrugBank database. Finally, nine broad-spectrum, novel drug targets were introduced. Acetate kinase (Ack) was selected as a novel target for drug discovery procedure due to the crucial role of this protein in the survival of P. gingivalis. Subsequently, structure-based virtual screening revealed six lead compounds with the most desirable features. Neoagarohexaose, Lucensomycin, Tetrafibricin, Naquihexcin_H, Tetramycin_A, and Platensimycin_D. Interestingly, Platensimycin_D1 had highest drug-likeness features in comparison to other lead compounds. While, Tetramycin_A and Lucensomycin showed better ADMET properties. The hit compounds identified here would be an initial compounds for experimental susceptibility testing against this pathogen. In addition, these findings might help out with the future studies on development of new therapeutic agents against P. gingivalis.