The development of neuroprotective drugs through eco-friendly production routes is a major challenge for current pharmacology. The present study was carried out to synthesize gold nanoparticles (AuNPs) through biogenic route using ethanolic bark extract of Terminalia arjuna, a plant of high interest in Asian traditional medicine, and to evaluate its neuroprotective effects. The synthesized AuNPs were characterized by UV-Vis spectroscopy, FTIR spectroscopy, XRD, FESEM, EDX, HRTEM, DLS, and zeta potential analyses. UV-Vis spectroscopy showed a characteristics SPR absorption band at 536 nm specific for AuNPs. XRD, TEM, and FESEM analyses revealed the formation of face-centered cubic crystalline, spherical and triangular shaped AuNPs, with size ranging between 20 and 50 nm. DLS and ZP analysis illustrated that the average size of AuNPs was 30 nm, which was found to be stable at 45 mv. The neuroprotective potential of AuNPs was evaluated by assessing its antioxidant, cholinesterase inhibitory, and antiamyloidogenic activities. AuNPs showed dose-dependant inhibition of acetylcholinesterase and butyrylcholinesterase with IC₅₀ value of 4.25 ± 0.02 and 5.05 ± 0.02 μg/ml, respectively. In vitro antioxidant assays illustrated that AuNPs exhibited the highest reducing power and DPPH radical scavenging activity. In addition, AuNPs also efficiently suppressed the fibrillation of Aβ and destabilized the preformed mature fibrils. Results of toxicity studies in PBMC and adult zebra fish illustrated that AuNPs are non-toxic and biocompatible. Overall, our results highlighted the AuNPs promising potential in terms of antioxidant, anticholinesterase, antiamyloidogenic effects, and non-lethality allowing us to propose these nanomaterials as a suitable candidate for the development of drugs helpful in the treatment of neurodegenerative disorders like Alzheimer's disease. Graphical abstract ᅟ.