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<i>Dracocephalum heterophyllum</i> (<i>D. heterophyllum</i>) is a traditional Chinese Tibetan medicine that has been used for the treatment of lymphitis, hepatitis, and bronchitis. However, only a few selected chemical components are currently obtained from <i>D</i><i>. heterophyllum</i>, which limits its further pharmacological applications. In this study, we have obtained samwinol from <i>D</i><i>. heterophyllum</i> by medium- and high-pressure liquid chromatography separation for the first time. Thereafter, we investigated the protective actions of samwinol against amyloid beta protein fragment 25–35 (Aβ_25–35) induced neurotoxicity in cultured rat pheochromocytoma PC-12 cells and explored its underlying mechanisms of action. The results indicated that samwinol could increase cell viability and inhibit the production of reactive oxygen species (ROS) and mitochondria-derived ROS, as assessed by MTT assay, Giemsa staining, and flow cytometry assay. Through Western blot analysis, it was found that samwinol substantially inhibited the phosphorylation of ERK(1/2) and promoted the expression of HO-1 and Nrf2. The data obtained from molecular docking were also consistent with the above conclusions. All of these results showed that samwinol from <i>D. heterophyllum</i> can display significant anti-neuroinflammatory and antioxidant activities in vitro, which are associated with the suppression of ERK/AKT phosphorylation and the activation of the Nrf2/HO-1 signaling pathway. In the future, additional in-depth mechanism studies will be carried out to provide more evidence for the potential of samwinol in the treatment of Alzheimer’s disease.