Glaucium species (Papaveraceae) are the medicinal plant that has been used traditionally to have been used for centuries to treat memory impairment. The aim of this study is to investigate the G. acutidentatum methanol and water extracts' phytochemicals and neuroprotective, anti-inflammatory, anti-mutagenic and anti-genotoxic potentials. Chemical composition was screened by using capillary gas chromatography–mass spectrometry (GC–MS). Neuroprotective effect was analyzed on nerve growth factor (NGF) differentiated-PC12 (dPC12) cells from neuroinflammation and neurodegeneration. Also, these extracts were screened for the mutagenic and anti-mutagenic activity by the Salmonella/microsome test system. In addition, genotoxic profiles and anti-genotoxic effects of these extracts were also analyzed by Comet technique. Extracts of G. acutidentatum had strong neuroprotective effects against hydrogen peroxide (H2O2)-induced damage. Also, neurite length was dose-dependently increased in extracts exposed groups compared with the H2O2-treated group. The anti-inflammatory effect of these extracts was parallel to neuroprotective effect. However, these extracts showed strong anti-mutagenicity (72.9–75.0%) and anti-genotoxic properties. Any genotoxic effect was observed of these extracts in lymphocyte cells, analyzed by the Comet assay. These results suggest that methanol and water extracts of G. acutidentatum had neuroprotective and anti-mutagenic effects and contained protective substances that decreasing damage to genetic material. •G. acutidentatum methanol and water extracts show neuroprotective activity.•G. acutidentatum methanol and water extracts show anti-inflammatory effect.•G. acutidentatum methanol and water extracts show anti-mutagenic effect.•G. acutidentatum methanol and water extracts show anti-genotoxic effect.