<abstract> <p>In the presented work, we aimed to investigate the antioxidant and possible neuroprotective capacity of extract of the aerial parts of <italic>Hypericum alpestre</italic>, found in high altitude Armenian landscape. The neuroprotective activity was evaluated using BV-2 wild type (WT) cells and acyl-CoA oxidase 1 (ACOX1) deficient (<italic>Acox1<sup>-/-</sup></italic>) microglial cell lines. In the chemical-based tests, <italic>H. alpestre</italic> extract showed high antioxidant activity, which was maintained even after heat treatment at 121 °C for 30 min. MTT test showed that the sub-cytotoxic concentration of investigated extracts for both microglial cell lines was 40 µg/mL. There were no significant changes in catalase activity during all period of treatment in both cell lines, meanwhile, SOD activity increased (up to 30%) in WT cells during the 48 h treatment. Increase of SOD activity (up to 50%) in Acox<sup>-/-</sup> cells was observed under the 24 h treatment. Significant modulation in activity of palmitoyl-CoA oxidase 1 was noticed only during the 48 h treatment of WT microglial cells. These results evidenced the pro-oxidant activity of the investigated extract. This finding can serve as a basis for further evaluation of plant extracts influence on cancer cell lines.</p> </abstract>