Tumor necrosis factor-α (TNF-α) is a major cytokine involved in the inflammatory response. Elevated TNF-α expression has been found to be associated with the development of diabetes, septic shock, tumorigenesis, cardiovascular diseases, rheumatoid arthritis and inflammatory bowel disease. In the past decade, the success of anti-TNF-α biologics has valuated the importance of the blockade of TNF-α production in the treatment of patients with various inflammatory diseases. Oxidative stress is another important element in oxidative/inflammatory responses that directly linked to oxidation of proteins, DNA and lipids. The increased oxidant levels could activate nuclear factor-kappaB (NFκ-B), signal transduction and gene expression of TNF-α, interleukin-1 (IL-1) and other pro-inflammatory cytokines. Therefore, TNF-α inhibitors with anti-oxidative stress activity may have multiple target effect that could exhibit excellent anti-inflammatory activities. The review briefly highlights the pathological roles of TNF-α and oxidative stress in inflammation, and covers those natural products as TNF-α inhibitors capable of anti-oxidative stress activity.