Alzheimer’s disease is the leading cause of dementia among aging population. Currently accepted treatments are focused on the symptoms while efforts are made to the develop therapies that target the major pathological hallmarks i.e., β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles. Evidence from epidemiology and neuroimaging studies suggest that Type 2 Diabetes (T2DM) and Alzheimer's disease (AD) have a shared pathogenesis. Moreover, insulin resistance has been shown to impact hyperphosphorylation and aggregation of Tau making this an important risk factor for the detection of early AD. Therefore, an emerging body of research and clinical trials have focused on evaluating the therapeutic potential of the insulin-sensitizing drug Metformin in the treatment of AD. However, the mechanisms by which Metformin might impact Tau pathology and the long-term effect of this drug on cellular environment needs to be investigated thoroughly. Methodology and Results: For this study SHSY5Y cells are cultured in high-glucose media and investigated whether Metformin can impact total and phospho-tau levels. We observed that with an increasing dosage of Metformin there was a significant decrease of hyperphosphorylated Tau (Ser199/202 and AT8) compared to untreated controls despite an increase in total Tau levels which is again validates in transiently transfected with Tau-wild-type and E14 (pseudo-hyperphosphorylated) mutants. Conclusion: Metformin at a high dosage significantly decreases Tau hyperphosphorylation at disease epitopes that might be beneficial to AD. Our preliminary data also suggests that an insulin-responsive cellular environment can decrease Tau expression overall although further research is needed to delineate the underlying mechanistic pathways.