Green synthesis of nanoparticles has emerged as an effective and environmentally friendly method. Therefore, the current investigation is based on the green synthesis of zinc oxide nanoparticles (ZnO-NPs) using plant extract of () that act as a capping and reducing agent. is a fast-growing shrub and densely available plant and may have potential to synthesize ZnO-NPs. The synthesized ZnO-NPs were characterized by different techniques, including Fourier transform infrared spectroscopy (FT-IR), UV-visible (UV-Vis), energy-dispersive X-ray (EDX), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The UV-Vis spectrum at 350 nm revealed an absorption peak for the synthesis of ZnO-NPs. In addition, photoactive biomolecules of the prepared ZnO-NPs were identified by using FT-IR spectroscopy. Furthermore, the spherical geometry of ZnO-NPs was evaluated by SEM images. The synthesized ZnO-NPs were also used to enhance the antidepressant activity and exhibited a remarkable reduction in the time of immobility in tail suspension tests (TST) and forced swim tests (FST), as well as increased the BDNF levels in the brain and plasma. ZnO-NPs have a low risk of biocompatibility (cell visibility) at a concentration of 7 g/mL or below. The nanoparticles were biologically compatible when the concentrations were increased up to 11 g/mL. It was concluded that ZnO-NPs were investigated as a possible carrier for antidepressant drug delivery into the brain, and their excellent cytotoxic activity was evaluated by using the MTT assay to determine their biocompatibility.