Fruits from several Australian Syzygium species were common foods sources for the first Australians and are gaining increasing popularity in commercially available foods. They also had roles as traditional bush medicines although their antiseptic potential has not been rigorously studied. The antimicrobial activity of extracts of brush cherry (Syzygium australe) and riberry (Syzygium leuhmannii) fruit were investigated against a panel of bacteria and fungi involved in food spoilage and food poisoning to assess their potential as natural preservatives. Toxicity was also assessed using the Artemia franciscana nauplii bioassay. Fruit extracts of both species displayed good broad spectrum antibacterial activity although S. australe extracts generally had greater efficacy than the S. leuhmannii extracts. S. australe and S. leuhmannii fruit extracts inhibited the growth of the majority of the bacteria tested. In contrast, none of the extracts was an effective inhibitor of fungal growth. The inhibitory bioactivity of S. australe and S. leuhmannii fruit extracts against the bacterial panel validate the use by indigenous Australians of S. australe and S. leuhmannii as antiseptic agents and confirms their medicinal potential. Furthermore, the potential of these fruits as natural food preservatives is indicated as the extracts were effective at blocking the growth of bacteria associated with food spoilage.