The present study describes potential beneficial and adverse effects of plant-extract synthesized gold nanoparticles (AuNPs) on ethanol toxicity in SH-SY5Y cells. Although kudzu root extract (K), edible-gum extract (G), alone or in combination (KG), reduced Au3+ into AuNPs, the extract’s composition and the reaction temperature determined their size (AuNPKG(90<50<37) << AuNPK
(90,50<37) < AuNPG
(90<50); the subscript KG, K, or G is extract identification and numerical vales are reaction temperature in Celsius) and biological properties (AuNPKG
(90,50>37) << AuNPK
(90,50>37) < AuNPG
(90,50)). The surface of each AuNP contained the extract’s active ingredients, that were analyzed and confirmed using laser desorption ionization (LDI)) and low-matrix laser desorption-ionization (LMALDI). AuNPKG-50 was (i) least toxic to SH-SY5Y cells, but most effective in suppressing the adverse effects of ethanol on SH-SY5Y cells, and (ii) more effective than a combination of free kudzu and gum extracts. The beneficial and adverse effects of AuNPs may have been modified by the formation of proteins corona. This study provides a proof of concept for possible application of plant-extract synthesized AuNPs in mitigating ethanol toxicity.