Background: Amyloid-β peptide (Aβ) is involved in the formation of senile plaques in Alzheimer’s disease (AD), and causes neuronal cell death by inducing oxidative stress. Objective: We investigated the protective effect of Eremostachys labiosiformis extract against the Aβ-induced toxicity in SH-SY5Y cells. Methods: Methanolic extract from the aerial parts of E. labiosiformis was prepared by percolation method at room temperature. SH-SY5Y cells were treated and incubated with different concentrations of the extract for 1 h, before addition of Aβ. Cytotoxicity was measured 24 h after the addition of Aβ to the medium using MTT and reactive oxygen species (ROS) assays. Effective doses were evaluated using real-time polymerase chain reaction to evaluate expression of miR-212 and miR-132. The results were analyzed using SPSS software (16). Results: Exposure of ­SH-SY5Y cells to Aβ significantly affected the viability of cells and increased ROS levels. The results revealed that 1.2 and 2.5 μg/mL of the E. labiosiformis extract reduced Aβ-induced deterioration. Only 2.5 μg/mL of the extract could reduce ROS levels. In addition, 5 μg/mL of the extract increased the expression of the miRNAs, which was reduced after exposure to Aβ. Conclusion: Based on the antioxidant and protective effects of the E. labiosiformis extract on expression of miR-132 and miR-212 and ROS level, this herb could be used as a suitable candidate for future studies on neurodegenerative diseases including AD.