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Methamphetamine causes cytotoxicity and apoptosis in different cell lines. It seems that Descurainia sophia oil, as an East Asian folk herbal drug, can suppress the methamphetamine-induced cell death. In this study, protective effects of Descurainia sophia oil were followed up in methamphetamine-induced cell cytotoxicity in a neuron-like PC12 cell line. The viability, proliferation, and cytotoxicity of the cells were assessed by Trypan blue, MTT test, and lactate dehydrogenase (LDH) assay, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test was performed to detect DNA fragmentation and apoptosis. Nitric oxide (NO) level was detected by Griese method. Interleukin-1β (IL-1β), IL-6, interferon gamma (INF-γ), and tumor necrosis factor alpha (TNF-α) pro-inflammatory cytokines were measured by Rat Kit V-Plex, and finally, caspase-3 activity was determined by spectrophotometry. Results showed that Descurainia sophia oil has cell death–suppressing effects on PC12 cells. It enhanced the cell viability and proliferation and also increased the cell cytotoxicity and cell death index in methamphetamine-treated PC12 cells. Also, it suppressed NO production, inflammatory cytokine production by flow cytometry, mitochondrial membrane depolarization, and caspase-3 activity in a dose-dependent manner. We concluded that Descurainia sophia oil suppresses the methamphetamine-induced cell death in PC12 cell due to reduction of NO production, inflammation, and inhibition of apoptosis cascade. [ABSTRACT FROM AUTHOR]