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The medicinal plant, Syzygium guineense (Willd.) DC mediated green silver nanoparticles (SyG-Ag NPs) were successfully synthesized for the first time in Ethiopia. The synergistic influence of biomolecules of the plant leaf extract such as alkaloids, phenolic compounds, tannins, saponins and glycosides with Ag NPs towards the antibacterial activity has been investigated. The synthesized nanoparticles were characterized by UV-Vis, UV-DRS, FT-IR, XRD, SEM, EDXA, TEM, HRTEM and SAED techniques. The presence of absorbance maxima, λmax at 452 nm confirms the formation of SyG-Ag NPs. The energy gap, Eg of NPs, was found to be 2.1 eV. FTIR spectra confirmed the presence of biomolecules in the extract and NPs. The presence of 4 sharp peaks in the XRD pattern of NPs confirmed highly crystalline nature of NPs. The purity of the NPs was confirmed by SEM-EDAX analysis. The average particle size of NPs was found to be 27.62 nm. TEM-HRTEM-SAED analysis resulted in d-spacing values of 0.2396 nm which corresponds to Ag (111) lattice fringes of SyG-Ag NPs. The d-spacing value of the derived diffraction planes from 4 major spots; d111Ag = 0.2428 nm, d200Ag = 0.2056 nm, d220Ag = 0.1483 nm and d311Ag = 0.1263 nm, are in agreement with the XRD data. The antibacterial test results showed synergistic effect against both Gram positive bacteria, S. aureus (11±0.04 mm), and Gram negative bacteria E. coli (12±0.012 mm), P. aeruginosa (10±0.1 mm), and E. aerogenes (13±0.032 mm), respectively, proving potentiality of SyG-Ag NPs as a remedy for infectious diseases caused by tested pathogens.