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Nowadays, the biosynthesis of metal nanoparticles, particularly from plants, has been gaining interest. In the present work, the methanolic extracts of leaves, fruits, and the pollen grains of <i>Sabal blackburniana</i> were used for the green synthesis of ZnO nanoparticles, which were early detected by the formation of precipitate and further confirmed by UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy and zeta potential (ZP) studies. TEM analysis has shown different shapes, predominantly irregular small spherical narrow particles included in hexagonal structures with size ranging from 2.23 to 49.56 nm. The XRD pattern confirmed that all synthesized ZnO nanoparticles have wurtzite hexagonal structure with crystalline nature. The average particle crystallite sizes were 47.21, 47.67 and 47.8 nm. The UV-visible spectra showed <i>λ</i> <sub>max</sub> in the range of 354-368 nm, which indicated the presence of ZnO nanoparticles. The FT-IR analysis identifies the characteristic functional groups present on the surface of ZnO nanoparticles. The ZP determination demonstrated that all representative selected synthesized ZnONPs exhibited acceptable ZP values of -30.8 to -45.9 mV, which indicated their good stability. In addition, the anti-Alzheimer potential of the selected extracts and ZnONPs was evaluated by assessing acetylcholinesterase inhibitory activity <i>in vitro</i> according to the improved Ellman method. The results indicated that the selected extracts have acetylcholinesterase inhibitory activity, and highlighted the promising inhibitory potential of green-synthesized ZnONPs using pollen grains, fruits and leaves extracts; they exhibited a potent inhibitory effect with IC<sub>50</sub> values 63.78 ± 1.04651, 81.985 ± 3.075 and 117.95 ± 6.858 ng ml<sup>-1</sup> respectively in comparison to donepezil as standard (IC<sub>50</sub> = 50.7 ± 5.769 ng ml<sup>-1</sup>). Dereplication analysis of the selected extracts was performed using LC-MS; metabolic profiling revealed the presence of 41 compounds belonging to various chemical classes: flavonoids, steroidal saponins, terpenoids, alkaloids, lignans, sterols and fatty acids. Docking these dereplicated metabolites against the human AChE showed that the non-glycosylated flavonoid class of compounds was able to achieve interesting binding modes inside the AChE active site; they are suggested to be associated with the observed anti-AChE activity of <i>Sabal</i> extracts. This study is the first report to shed light on the acetylcholinesterase inhibitory activity of green-synthesized ZnO nanoparticles of <i>S. blackburniana</i> metabolites.