The methanolic extract and fractions from the stem bark of Tridesmostemon omphalocarpoides were investigated for their in vitro antimicrobial properties as well as their phytochemical constituents. The stem bark was collected from Yaoundé, in the Centre Province of Cameroon. The antimicrobial activity of the extract and fractions against two Candida species and seven aerobic bacteria was evaluated on the basis of the inhibition zones (IZ) using agar hole diffusion method, the minimal inhibition concentration (MIC) and the minimal microbicidal concentration (MMC) by the macrodilution method. The results indicated significant anticandidal and antibacterial effect of the methanolic extract and fractions against all the nine microorganisms tested. Preliminary phytochemical analysis of methanolic extract showed the presence of biologically active components namely alkaloids, steroids, tannins, saponins, phenols, polyphenols and flavonoids. The acute toxicity of the methanolic extract was also studied. This was found to be non-toxic to the inbred Wistar rats treated per os. The results of this study suggested that the stem bark of this plant could be safely used in the treatment of some infectious diseases.