Streptococcus mutans and Streptococcus sobrinus have been implicated as the primary causative agents of dental caries in humans. This study aimed to screen the antibacterial activity of the n-hexane, ethyl acetate, methanol, and aqueous extracts of Ginger against mentioned bacteria and investigate chemical constituents of the extracts, and their activity against some drug targets in S. mutans. Antimicrobial tests including biofilm inhibition, time-kill kinetics, and adherence inhibition alongside cytotoxicity of extracts, were assessed. A molecular networking technique was used to find chemical constituents of the extracts. Molecular docking analysis on the Schrodinger package was applied to identify the binding interactions of the compounds to targeted enzymes. Methanol and ethyl acetate extracts showed the highest antibacterial activity against S. mutans and S. sobrinus. Different compounds including polyphenols, alkaloids, anthraquinones, flavonoids, terpenoids, glycosides, steroids, and reducing sugars dereplicated from Ginger extracts. The binding affinity of ligands with free hydroxyl groups was better than other ligands against all tested enzymes. This study introduces a wide range of Z. officinal extracts compounds to be used in different drug discovery studies. Some Ginger compounds with high affinity to investigated enzymes can be considered as candidate compounds for anti-caries drug development studies.Communicated by Ramaswamy H. Sarma.