Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer’s disease. The present paper’s goal was to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. We treated the human neuroblastoma SH-SY5Y cell line with A{\beta }_{1-42} as an Alzheimer’s disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. Further, SH-SY5Y cells damaged by A{\beta }_{1-42} were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against A{\beta }_{1-42}-induced toxicity. Results showed that Akt and mTOR’s geniposide inhibited phosphorylation induced by A{\beta }_{1-42,} enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by A{\beta }_{1-42}. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against A\beta toxicity.