Stem bark and root of Khaya senegalensis were extracted with ethyl acetate and n-Hexane and extracts screened for metabolites, antibacterial activity. There were also used to reduce AgNO3 to synthesize AgNPs and their antibacterial effects studied. A number of metabolite example flavonoids, steroids, tannins etc were discovered. The stem bark extract show higher activities on all the four bacterial isolates compared to the root extract: on K. pneumoniae (28.1±0.42), B. subtilis (20.1±1.21).while the root extract show lower activity on the test organisms at 26.3± 0.12 on K. pneumoniae and 22.1±0.20 on S. epidermidis. The activities of the nanoparticles are higher than those of the crude extracts and standard antibiotics used as control. The zones of inhibition around the bacterial colonies by the particles are far wider around each organism challenged. AgNPs bark extract on B. subtilis produced 31.2±0.11zone of inhibition of 24. 24.3±1.21 and 28.2±2.12 by Streptomycin and Tetracyclines. Strikingly, both the ethyl acetate and n-Hexane bark extracts of the plant demonstrated higher activities on the test isolates compared to the root extracts but the nanoparticles of the root had more activity compared to the stem bark. The activity of the metabolites in the root may have been enhanced when they were carried by the nanoparticles. The potency of Khaya senegalensis on microbial pathogens may be broadened when processed into its nanoparticles. Keywords: Synthesis; silver nanoparticles (AgNPs); stem bark; African mahogany; comparative studies.