The need for alternative treatment of infections caused by vancomycin-resistant Enterococci (VRE) is of global concern. This study used Azanza garckeana (AG) seeds to synthesize silver nanoparticles (AgNPs) with anti-VRE activity. The nanoparticles were characterized using UV-Vis, FTIR, SEM, and EDXRF. Antimicrobial activities, MIC, and MBC were evaluated by agar well and microtiter dilution, respectively. UV-spectroscopy confirmed the presence of peaks at 435 nm for spherical AgNPs. FTIR spectrum showed sharp peaks at 3441, 2936, 2859, 1640, and 1385 cm−1, indicating the presence of hydroxyl, methyl, methylene, alkenyl, and alkyl groups in the AgNPs. SEM and EDXRF results revealed particles with clustered crystalline patterns and silver as the highest element present, with nickel also present in very minute amounts. The AgNPs exhibited inhibitory activity against the VRE species at both 50 and 100 µg/ml. Also, MIC values varied between 12.5 µg/ml and 25 µg/ml, while MBC values were 50 µg/ml and 25 µg/ml respectively. Conclusively, A. garckeana AgNPs demonstrated potent antimicrobial activity, suggesting their antimicrobial properties could be utilized in a variety of biomedical applications.