Alzheimer’s disease is asignificant cause of elderly mortality, requiring global efforts to develop effective treatments. Recent research highlights the potential of medicinal plants with high antioxidant capacity to slow down the progression of diseases. Guided by Thai traditional drugrecipes, this study evaluates medicinal plants traditionally regarded as “life-longevity elixirs” for antioxidant and neuroprotective properties against oxidative stress-induced neurotoxicity. Four plant species were selected and screened: Acanthus ebracteatus Vahl,A lbizia procera (Roxb.) Benth., Diospyros rhodocalyx Kurz and Piper sarmentosum Roxb. Total phenolic and flavonoid content were quantified alongside antioxidant screenings using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Extracts with strong antioxidant activities were furthertested for neuroprotective effects in SH-SY5Y neuroblastoma cells. The ethanolic extracts of A. procera (AP) andP. sarmentosum (PS) showed the highest antioxidant activities in both DPPH andABTS assays, with IC50 values of 54.36 ± 5.55 and 61.65 ± 4.73 μg/mL in the DPPH assay, and 31.38 ± 4.19and 37.25 ± 1.68 μg/mL in the ABTS assay, respectively. After inducing oxidative stress in SH-SY5Y with H2O2 and measuring cell viability with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 68.76 ± 0.72% of cells survived. Ascorbic acidprevented cell death up to 95.64 ± 1.07%. AP at 10 μg/mL protected 85.15 ± 1.68% of cells, while PS at 1 μg/mL protected 82.48 ± 0.83%of cells. This study highlights the potential of Thai medicinal plants; A. procera and P. sarmentosum for their antioxidant and neuroprotective effects. Their substantial protection against oxidativestress-induced neurotoxicity supports further exploration as potential candidates for neurodegenerative disease therapies.