In the last years, there has been an alarming increase in antibiotic resistance by pathogenic microbes, which has become a major public health concern. There is a great interest in developing new antimicrobial for reducing the impact. Silver nanoparticles (AgNPs) as antibacterial agents are currently being studied to be used to fight these pathogenic microbes. The aim of the present study was to synthesize AgNPs of different sizes through the use of microwave and determine their antimicrobial activities. Synthesis of sizedependent L-glutathione-capped spherical nanoparticles through one-pot microwave synthesis was achieved, and their antimicrobial properties were determined. Different sizes of AgNPs between 5-10, 15-35, and 50-80 nm were made by varying the concentration of silver nitrate and using sodium borohydride (NaBH 4 ) as a reducing agent. L-glutathione was used to stabilize the AgNPs to prevent them from aggregation in the colloidal solution.The synthesized AgNPs showed ultraviolet absorption at around 400 nm with high concentration of AgNO 3 having sharp peaks. The formed particles were crystalline in nature with uniform spherical shape. The formed AgNPs were of crystalline size of 9. 94, 18.45, 34.96, 52.40, and 58.50 nm. Fourier transform infrared analysis confirmed conjugation of glutathione as a capping agent to AgNPs as the result of the formed spectra showing the absence of ─SH stretch. The high temperature generated by microwave helped to synthesize nanoparticles within a short time and by varying the concentration of AgNO 3 helped obtain the desired particle size. Glutathione conjugated well with AgNPs as a result of interaction of negative thiol resulting to colloidal stabilization and reduced aggregation. The antibacterial activity of AgNPs was found to be size dependent with the smaller size of 9.94 nm being more efficient than 18. 45, 34.96, 52.40, and 58.50 nm against the tested strains Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC 25922), Salmonella spp. (ATCC 700623), and Staphylococcus aureus (ATCC 25923). Of the four stains, E. coli was found to be the least affected by all three different particle sizes of the synthesized AgNPs.