In the last decades, plant extracts have received great attention. In particular, many studies pointed out the potential neuroprotective effect of polyphenols-rich extracts from plants. Evidence indeed highlights the action of polyphenols, both as antioxidants and as inhibitors in the formation of amyloid protein aggregates, known to be involved in neurodegenerative diseases. In this work, aqueous extracts obtained at high and room temperature from leaves of Moringa oleifera (MO) harvested in Sicily were characterized for polyphenolic content, anti-oxidative and free radical scavenging capacity. UHPLC-HESI-MS analysis shows that both water extracts are rich in terms of polyphenols. Then, MO aqueous extracts were tested as inhibitors in the amyloid aggregation process of Amyloid β-peptide 1-42 (Aβ(1-42)). This peptide is strongly involved in Alzheimer's disease (AD), its overproduction and aggregated species being considered a hallmark of AD. Results show that MO extracts cause a strong inhibition on the amyloid process. Biophysical characterization of the extracts reveals the presence of stable polyphenol assemblies. Both free and aggregated polyphenols elicit an efficient inhibition mechanism held up by their ability to interact with metastable species, strongly hindering autocatalytic amyloid growth. Finally, the effects of the MO room temperature extract have been tested on an AD cell model, retinoic acid-differentiated SH-SY5Y cells challenged with glyceraldehyde (GA). Cell pretreatment with MO extract results in an improved cell viability in comparison with the control and furthermore in the reduction of both mitochondrial reactive oxygen species and GA-stimulated Aβ(1-42) production.