Certain nutrients are able to exert health promoting effects. The consumption of Brassicaceae vegetables has increased given their reported beneficial effects on human health, due to their high content of nutraceutical compounds. The health benefits appear to be associated with the presence of glucosinolates and flavonoids. Certain nutraceutics have been revealed to have anti-inflammatory action. In the present study, the anti-inflammatory properties of Eruca sativa seed extract (ESE) were evaluated in NSC-34 motor neurons exposed to the cell culture medium of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Treatment with LPS-stimulated RAW 264.7 medium induced apoptosis and the expression of Toll-like receptor 4 (TLR4) and cyclooxygenase 2 (COX2) in NSC-34 motor neurons. Additionally, the stimulation of NSC-34 motor neurons with the medium of LPS-treated macrophages triggered the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome proteins and the production of pro-inflammatory cytokines. Pre-treatment with ESE counteracted the apoptosis and production of pro-inflammatory cytokines in NSC-34 motor neurons treated with the medium of LPS-treated RAW 264.7. It also eliminated COX2 and TLR4/NLRP3 inflammasome expression. In addition, pre-treatment with ESE was able to restore interleukin 10 expression in NSC-34 cells. These results demonstrate the anti-inflammatory and neuroprotective effects of ESE.