Curcuma zedoaria is a medicinal plant rich in secondary metabolites with reported antioxidant and pharmacological properties. However, the potential biomedical application of plant-derived bioactive compounds may be constrained by challenges associated with their delivery and bioavailability. Plant-mediated nanoparticle synthesis offers an approach for developing nanomaterials that warrant further investigation as potential delivery platforms for bioactive constituents. This study evaluated the phytochemical composition of an ethanolic extract of C. zedoaria, the acute toxicity of the test preparation, and the physicochemical characteristics and in vitro antioxidant activity of C. zedoaria-mediated zinc oxide nanoparticles (ZnO-NPs). Preliminary quantitative phytochemical screening was performed on the extract, while ZnO-NPs were prepared using the green synthesis precipitation-based method involving the freshly prepared aqueous plant extract. Acute toxicity was evaluated in experimental animals following oral administration. Nanoparticle crystallinity and elemental composition were assessed using X-ray diffraction (XRD) and energy-dispersive X-ray (EDX) spectroscopy, respectively. Antioxidant activity was investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and ferric reducing antioxidant power (FRAP) assays. The extract contained several phytochemical groups, with alkaloids and terpenoids among the most abundant constituents (17.05 ± 0.19 and 17.05 ± 0.01 mg/mL, respectively), followed by phenols (16.82 ± 0.02 mg/mL) and flavonoids (13.30 ± 0.13 mg/mL). No mortality or observable adverse reactions were recorded up to 5000 mg/kg body weight under the conditions of the oral acute toxicity assessment. XRD analysis confirmed crystalline ZnO-NPs, with an estimated average crystallite size of 12.39 nm, while EDX revealed prominent zinc and oxygen signals. The ZnO-NPs exhibited concentration-dependent DPPH radical-scavenging activity, reaching 67.47% inhibition, with a reported IC₅₀ of 0.10 µg/mL. FRAP activity also increased with concentration, reaching 1.21 ± 0.00 mg ascorbic acid equivalents (AAE) at 250 µg/mL. These findings demonstrate the phytochemical richness of C. zedoaria and the potential of its extract as a biological component in the preparation of crystalline ZnO-NPs with measurable in-vitro antioxidant activity. The findings provide a basis for further investigation of their safety, formulation characteristics, bioavailability, and release behaviour before determining their suitability for specific biomedical applications.