Aims: To optimize effects of selected process parameters affecting yield of green synthesized silver nanoparticles and their antibacterial activity. Study Design: Study was designed with 3 factors Box Behnken Design (Minitab 17) and Response optimizer (Minitab 17) was used to determine optimum values of the factors. Place and Duration of Study: Department of Microbiology, Federal University of Technology, Owerri, Nigeria, from March to November, 2020. Methodology: After extraction by boiling, qualitative phytochemical analysis of leaves’ extracts of Ipeoma batatas, Commelina africana and Manihot esculenta was carried out. Following synthesis of silver nanoparticles as prescribed by Box Behnken design, yield of AgNPs was optimized with Response optimizer (Minitab 17). Then antibacterial activity of resulting AgNPs was tested against isolates of P. aeruginosa and E. coli. Results: Extracts contained alkaloids, tannins, proteins and amino acids, flavonoids and phenolic compounds, but no sterols and cardiac glycosides. Optimum pH, temperature and time obtained with Response Optimizer resulted in 62.6%, 55.8% and 54.9% increase in yield of AgNPs, with leaf extracts of C. africana, M. esculenta and I. batatas respectively, compared to un-optimized conditions. Absorbance for resulting AgNPs peaked between 380 to 400 nm. Zones of inhibition (mm) of P. aeruginosa with AgNPs synthesized using extracts of C. africana, I. batatas and M. esculenta were 10, 10 and 9 respectively, under un-optimized condition, and 12, 10 and 8 respectively, for optimized conditions. Against E. coli, they were 11, 11 and 12 for AgNPs synthesized with extracts of C. africana, I. batatas and M. esculenta respectively, under un-optimized condition, and 13, 9 and 11 respectively, for optimized conditions. Conclusion: Leaf extracts of C. africana, I. batatas and M. esculenta can be used in synthesizing AgNPs, with marked antibacterial activities. Box Behnken design is useful for optimization of effects of process parameters.