The current study presents the green fabrication of zinc oxide nanoparticles (ZnO-NPs) using the leaf extract of Ziziphus spina-christi and their protoscolicidal effects and hemocompatibility. The obtained nanoparticles were recognized by Ultraviolet-visible (UV–Vis) spectrometry, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) analysis. The present results confirmed the creation of ZnO-NPs as a spherical shape in SEM with an average particle size of about 83 nm and presented an absorption maximum at 355 nm in the UV-Vis data. EDS analysis confirmed the elemental composition and revealed strong signals for zinc and oxygen. XRD spectrum expressed the hexagonal wurtzite form with an average crystallite size of ~ 31.2 nm. The potential of in vitro protoscolicidal efficacy of ZnO-NPs was reported in this paper. The highest antiparasitic activity was at 400 μg / ml of ZnO-NPs after 60 min of the exposure period, with a 100% mortality of the treated protoscoleces. Several morphological alterations were observed on the protoscoleces by optical and scanning electron microscopy. The lysis of RBCs at various doses of ZnO-NPs was significantly less than the positive control, thus proposing its biocompatibility. This investigation suggests that phytochemicals like polyphenols in the extract of this plant act as reducing and stabilizing agents for the synthesis of ZnO-NPs, which showed promising biological activities. Further studies are required to investigate the ZnO-NPs scolicidial effects in the in vivo model. The present work's novelty is utilizing Z. spina-christi leaves extract as a substantial reducing and capping agent for ZnO-NPs fabrication. In addition, their antiparasitic and hemocompatibility were investigated.