<p>Excitotoxicity due to excessive glutamate release or impaired regulation of its levels causes neuronal damage and death, which has been implicated in various neurological disorders and brain injuries. In this study, we investigated the potential neuroprotective effects of Salviae Miltiorrhizae Radix (SMR) extract against glutamate-induced excitotoxicity in HT-22 cells, a hippocampal neuronal cell line. After treatment with glutamate alone or in combination with SMR extract, the cell viability, apoptosis, and reactive oxygen species (ROS) levels were analyzed. The results showed that the SMR extract significantly decreased the production of reactive oxygen species in HT-22 cells, which was accompanied by a decrease in nuclear condensation and apoptosis. Using the electrical impedance measurement, we monitored the increase in the resistance of 5&#xa0;mM glutamate-treated HT-22 cells with 25&#xa0;µg/mL SMR at 21.5&#xa0;kHz, which was comparable to the negative control group when the culture time was 96&#xa0;h. On the other hand, the resistance at the frequency of 21.5&#xa0;kHz for the cells exposed to the glutamate without SMR decreased and reached the initial value. Microscopic observation of cell morphology on the transparent indium tin oxide (ITO) electrodes supported the impedance analysis with or without SMR. Therefore, the impedimetric method was suitable for continuously recording the protective effect of the SMR extract on HT-22 cells against oxidative stress-induced cell damage.</p> Graphical Abstract <p>Electrical impedance characterization of the protective effect of Salviae Miltiorrhizae Radix on Glutamate-induced apoptosis</p> <p></p>