Biosynthesis of nanoparticles is the preferred route for the fabrication of biocompatible and cheaper drugs. In this study, the extract and major secondary metabolite from Helichrysum aureonitens, 3,5-dihydroxy-6,7,8-trimethoxyflavone, were used to synthesize silver and zinc oxide nanoparticles. Spectroscopic and microscopic techniques confirmed the formation of the nanoparticles. The flavone alone showed higher DPPH radical scavenging ability (IC50 = 487.1 mu g mL(-1)) relative to the control, butylated hydroxytoluene. In addition, silver nanoparticles synthesized using the flavone had higher ferric reducing potential (Fe3+ to Fe2+) compared to the other test samples. The cytotoxic activity of the plant extract, the flavone, and their biosynthesized nanoparticles was also investigated using the MTT assay against the cancerous MCF-7 (breast adenocarcinoma) and A549 (human lung adenocarcinoma)), and non-cancerous HEK293 (human embryonic kidney) cell lines. The plant extract decreased the cell viability of A549 (IC50 = 68.6 mu g mL(-1)) without being cytotoxic against HEK293, even at high concentrations. Silver nanoparticles significantly decreased cell viability of A549 and moderately decreased cell viability of MCF-7 but induced cell death of HEK293 even at low concentrations. This study provides a green synthesis route for silver and zinc oxide nanoparticles and confirms the therapeutic effectiveness of H. aureonitens, thereby validating its use in ethnomedicine.