ABSTRACT Introduction: Many species of Syzygium are known to have antiseptic activity. Australian Syzygium species had roles as traditional bush medicines for Australian Aborigines although their antiseptic potential has not been rigorously studied. Methods: The antimicrobial activity of methanolic extracts of Syzygium australe and Syzygium leuhmannii leaves was investigated by disc diffusion assay and growth time course assay against a panel of bacteria and fungi. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: S. australe leaf extract inhibited the growth of 10 of the 14 bacteria tested (71%). Gram-positive and Gram-negative bacteria were equally susceptible. 8 of the 11 Gram-negative bacteria (73%) and 2 of the 3 Gram-positive bacteria (67%) tested had their growth inhibited by S. australe leaf extract. The extract also displayed antifungal activity against a nystatin resistant strain of A. niger but did not affect C. albicans or S. cerevisiae growth. In comparison, S. leuhmannii leaf extract did not inhibit the growth of any of the microbial agents tested in the disc diffusion assay. The antibacterial activity of S. australe leaf extract was further investigated by growth time course assays which showed significant growth inhibition in cultures of A. hydrophilia, B. cereus, and P. fluorescens within 1 h but not of B. subtilis. S. leuhmannii also inhibited the growth of P. fluorescens and to a lesser extent, A. hydrophilia in the time course assay. Both Syzygium extracts displayed low toxicity in the Artemia franciscana bioassay. Conclusions: The low toxicity of these Syzygium extracts and the inhibitory bioactivity of S. australe against the bacterial panel validate Australian Aboriginal usage of S. australe leaves as antiseptic agents and confirms their medicinal potential.