Alzheimer’s disease (AD) is the most common neurodegenerative disorder, which is characterized by a progressive loss of neuronal cells in different brain’s regions, that lead to a functional cognitive impairment. Neurofibrillary tangle (NFT) is a primary biomarker of AD, which is formed by an abnormal accumulation of hyper phosphorylated Tau protein inside the neuronal cells. Effective treatment for neurodegenerative diseases (NDs) presents a clinical challenge. Natural products showed a promising role in treatment of neurodegenerative diseases (NDs). Geniposide is a natural extract from the fruit of Gardenia Jasminoides, which is known to have significant biological activities such as anti-inflammation, anti-oxidation, and anti-diabetic effects. In this project we aim to assess the ability of using Geniposide as a neuroprotective agent, and to identify the efficiency of Geniposide in preventing of tauopathy in human neuroblastoma cell line. Firstly, 300 μM zinc sulfate (for 4 hours) was used to establish an in vitro tauopathy model using SH-SY5Y cells. Then, we examined the neuroprotective ability of Geniposide using different concentrations (10-25-50-75-100 μM), all concentrations showed significant results with MTT assay. Next, we are studying the efficacy of Geniposide in the prevention of hyperphosphorylation of Tau protein. Geniposide decreases the hyperphosphorylated Tau significantly. We are also investigating the role of different protein kinases such as (PI3K, AKT, mTOR, GSK-3β, and p-Tau) to reveal the molecular pathway by which Geniposide works. Therefore, Geniposide is showing a promising therapeutic strategy for Alzheimer’s disease.