African toothbrush sticks have been used for centuries for maintaining oral hygiene. Seven different toothbrush sticks were acquired from Addis Ababa (Ethiopia); Clausena anisata, Dovyalis abyssinica, Maerua oblongifolia, Osyris quadripartite, Pittosporum viridiflorum, Sida cuneifolia and Stereospermum kunthianum. These have been screened for antimicrobial efficacy in an attempt to establish a scientific basis for their frequent use in maintaining oral hygiene. Minimal inhibitory concentrations (MIC) were determined on lipophilic and aqueous extracts against four Gram-positive bacteria (Bacillus cereus, Streptococcus mutans, Lactobacillus acidophilus and Staphylococcus aureus), two Gram-negative bacteria, (Escherichia coli and Klebsiella pneumoniae) and two yeasts (Candida albicans and Cryptococcus neoformans). Results indicate moderate to good antimicrobial activity for most pathogens studied with S. cuneifolia having the greatest overall antimicrobial efficacy with MIC values mostly ranging between 0.4 and 6.0 mg mL−1 for the solvent extracts. The aqueous extracts indicated similar or in selected samples better activities than the solvent extracts.