BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with poorly understood pathology. Elevated tau, phospho-tau and mitochondrial dysfunction are significantly correlated with an increased risk of AD and are therefore targets for disease-modifying therapy. In this study, we examined the effects of polyphenolic extracts from six different varieties of sorghum: Shawaya short black-1 (Black), IS1311C (Brown), QL33/QL36 (Red), B923296 (Red), QL12 (White), and QL33 (Red) on the attenuation of beta amyloid-induced phospho-tau levels, total tau levels, and mitochondrial dysfunction in neuronal cells. METHOD: Tau proteins (231 (pT231), Serine- 199 (pS199), and total tau proteins (T-tau)) were detected and quantified using sandwich ELISA kits, while mitochondrial dysfunction was measured in terms of mitochondrial membrane potential (Δψm) and adenosine triphosphate (ATP) levels. RESULTS: Almost all varieties of the sorghum extracts reduced the beta amyloid-induced pS199 and pT231 levels ( CONCLUSIONS: The polyphenol extracts from sorghum attenuated the tau toxicity and Aβ-induced mitochondrial dysfunction in a variety- and dose-dependent manner and made a promising disease-modifying agent against AD. However, extensive research is needed to validate the efficacy of the sorghum extracts prior to animal and clinical studies.