Introduction: Melodorum leichhardtii F.Muell. Benth. is a rainforest vine which is native to north-eastern rainforest regions of Australia. Melodorum spp. are rich in a variety of terpenoids with reported antibacterial activity. Despite this, M. leichhardtii leaf extracts have not previously been examined for bacterial growth inhibitory properties. Methods: The antimicrobial activity of a methanolic M. leichhardtii leaf extract was investigated by disc diffusion and growth time course assays against a panel of bacterial pathogens. The growth inhibitory activity was further quantified by MIC determination. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: The methanolic M. leichhardtii leaf extract was a potent inhibitor of Klebsiella pneumonia (MICs of 388μg/mL). The extract was also a low-moderate inhibitor of B. cereus growth (MICs 3678μg/mL) but was completely devoid of inhibitory activity against all other bacterial species tested. The antibacterial activity of the methanolic M. leichhardtii leaf extract was further investigated by growth time course assays that showed significant growth inhibition in cultures of K. pneumoniae and B. cereus within 1 h of exposure. All extracts were determined to be nontoxic in the Artemia franciscana nauplii bioassay, indicating their safety for use in preventing diseases caused by these pathogens. Conclusion: The lack of toxicity of the M. leichhardtii leaf extracts and their growth inhibitory bioactivity against K. pneumoniae and B. cereus indicate their potential in the development of new therapies targeting these bacteria.