Introduction: Closely related plant species often share similar secondary metabolites and bioactivities and are therefore good targets for bioactivity testing when one or more species within a genus are known to possess therapeutic properties. The genus Piper has a long history of medicinal usage in many areas of the world. Many Piper spp. are known to have therapeutic properties and several have antibacterial bioactivities. Methods: The ability of P. novae-hollandiae leaf extracts to inhibit the growth of a panel of bacterial pathogens was investigated by disc diffusion assay. Toxicity was examined using the Artemia franciscana nauplii bioassay. Results: P. novae-hollandiae methanolic and aqueous extracts were completely ineffective at inhibiting the growth of panels of gram-positive and gram-negative bacteria. The extracts were nontoxic or of low toxicity to Artemia nauplii following 24 h exposure. Conclusion: Despite the close taxonomic relationship with several bioactive Piper spp. and its therapeutic use by first Australians, P. novae-hollandiae leaf extracts were completely ineffective bacterial growth inhibitors. However, these extracts may have other therapeutic properties and testing against protozoa, fungi, virus and tumour cells is warranted.