Background: Inflammation in the central nervous system, resulting from a loss of control involving a network of neuronal cells, is foremost contributors to the instigation and advancement of major neurodegenerative diseases. Therefore, therapeutic strategies should restore back to a well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. Objective: The objective of this study is to evaluate the anti-neuroinflammatory potential of Capsaicin in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Materials and Methods: In this present study, we selected Capsaicin and investigated through cell-based-assay systems through the various cellular techniques enzyme-linked immunosorbent, immunoblot and immunofluorescence assays to identify anti-inflammatory effects. Results: We found that capsaicin exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced nitric oxide, tumor necrosis factor-α, interleukin-1 β, and interleukin expression from activated BV-2 microglia cells dose-dependently. On the intracellular level, capsaicin inhibited IκB-phosphorylation and subsequently nuclear Factor-κB (NF-κB)-translocation in microglia cells. Further, capsaicin blocked the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2. Further, capsaicin inhibits the increased production of pro-inflammatory responses in LPS-stimulated BV-2 cells by suppressing NF-κB activation. Conclusion: The significant inhibition of neuroinflammatory responses in stimulated microglial cells together indicate that capsaicin is a potential therapeutic agent and could possibly be used in the development of novel drug for the prevention and treatment of neuroinflammatory diseases.