Background:Nanoparticles are globally synthesized for their antimicrobial, anti-inflammatory, wound healing, catalytic, magnetic, optical, and electronic properties that have put them at the forefront of a wide variety of studies. Among them, zinc oxide (ZnO) has receivedmuchconsideration due to its technological and medicinal applications.In this study, we report on the synthesis process ofZnOnanoparticles using AthrixiaphylicoidesDC natural extract asareducing agent. Methods:Liquidchromatography-massspectrometry(LC-MS) was used to identify the compounds responsible for the synthesis ofZnOnanoparticles. Structural, morphological and optical properties of the synthesized nanoparticles have been characterized through X-raydiffraction (XRD),Ultraviolet-visible spectroscopy (UV-Vis),Fouriertransforminfrared spectroscopy(FTIR),scanningelectronmicroscopy (SEM) andenergy-dispersiveX-rayspectroscopy (EDS). Results:LC-MS results showedthat different flavonoids and polyphenols, as well as Coumarin, an aromatic compound, reacted with the precursor to formZnOnanoparticles. XRD and UV-Visanalysis confirmed the synthesis ofZnOnanoparticles, with a spherical shape showed in SEM images. The quasi-sphericalZnOcrystals had an average crystallite size of 24 nm. EDS and FTIR analysis confirmed that the powders were pure with no other phase or impurity. Conclusions:This study successfully demonstrated that the natural plant extract of A.phylicoidesDC. can be used in the bio-reduction of zinc nitrate hexahydrate to prepare pureZnOnanoparticles, thus, extending the use of this plant to an industrial level.