Staphylococcal and streptococcal species trigger a wide variety of infections involving epithelial tissues. Virginian witch hazel (WH; Hamamelis virginiana L.; family: Hamamelidaceae) is a plant that has been used traditionally by Native Americans to treat a variety of skin conditions. Extracts from the leaves were examined for their inhibitory effects on these bacterial species. Solvents of different polarity (water, methanol, ethyl acetate, hexane and chloroform) were used to prepare extracts from WH leaves, and the aqueous resuspensions were screened for antibacterial activities using disc diffusion and liquid dilution assays. Extract phytochemical profiles and toxicities were also examined, and combinations of extracts with conventional antibiotics were tested against each bacterial strain. The methanolic and aqueous extracts inhibited the growth of S. oralis, S. pyogenes, S. epidermidis and S. aureus, but not S. mutans. The extracts were especially active against staphylococcal species, with MIC values between 200 and 500 μg/ml. Combinations of active extracts with conventional antibiotics failed to yield beneficial interactions, except for two cases where additive interactions were observed (aqueous WH extract combined with chloramphenicol against S. oralis, and methanolic WH extract combined with ciprofloxacin against S. aureus). Phytochemical assays indicated an abundance of tannins, triterpenoids and phenolics in the water and methanol extracts, with trace amounts of these components in the ethyl acetate extract. Phytochemicals were not detected in hexane and chloroform extracts. Thus, phytochemical abundance in extracts was concordant with antibacterial activities. All extracts were found to be non-toxic in Artemia nauplii assays. These findings indicate the potential for WH leaf extracts for clinical use in treating staphylococcal and streptococcal infections, while substantiating their traditional Native American uses.