Ginger (Zingiber officinale Roscoe) has been used widely as a food spice and an herbal medicine. In particular, its gingerol-related components have been reported to possess antimicrobial and antifungal properties, as well as several pharmaceutical properties. However, the effective ginger constituents that inhibit the growth of oral bacteria associated with periodontitis in the human oral cavity have not been elucidated. This study revealed that the ethanol and n-hexane extracts of ginger exhibited antibacterial activities against three anaerobic Gram-negative bacteria, Porphyromonas gingivalis ATCC 53978, Porphyromonas endodontalis ATCC 35406 and Prevotella intermedia ATCC 25611, causing periodontal diseases. Thereafter, five ginger constituents were isolated by a preparative high-performance liquid chromatographic method from the active silica-gel column chromatography fractions, elucidated their structures by nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry and their antibacterial activity evaluated. In conclusion, two highly alkylated gingerols, [10]-gingerol and [12]-gingerol effectively inhibited the growth of these oral pathogens at a minimum inhibitory concentration (MIC) range of 6-30 microg/mL. These ginger compounds also killed the oral pathogens at a minimum bactericidal concentration (MBC) range of 4-20 microg/mL, but not the other ginger compounds 5-acetoxy-[6]-gingerol, 3,5-diacetoxy-[6]-gingerdiol and galanolactone.