Pteleopsis hylodendron (Combretaceae) is used in Cameroon and West Africa folk medicine for the treatment of various microbial infections (measles, chickenpox, and sexually transmitted diseases). The antibacterial properties of the methanolic extract and fractions from stem bark of Pteleopsis hylodendron were tested against three Gram-positive bacteria and eight Gram-negative bacteria using Agar-well diffusion and Broth microdilution methods. Antioxidant activities of the crude extract and fractions were investigated by DPPH radical scavenging activity and β-carotene-linoleic acid assays. The methanolic extract and some fractions exhibited antibacterial activities that varied between the bacterial species (ID = 0.00-25.00 mm; MIC = 781-12500 μg/mL and 0.24-1000 μg/mL). The activity of the crude extract is, however, very weak compared to the reference antibiotics (MIC = 0.125-128 μg/mL). Two fractions (F(E) and F(F)) showed significant activity (MIC = 0.97 μg/mL) while S. aureus ATCC 25922 was almost resistant to all the tested fractions. In addition, the crude extract and some fractions showed good antioxidant potential with inhibition values ranging from 17.53 to 98.79%. These results provide promising baseline information for the potential use of this plant as well as some of the fractions in the treatment of infectious diseases and oxidative stress.