It is indicated that malvidin has anti‐inflammatory and antioxidant effects on various cells, although the function of malvidin in preventing inflammatory reactions caused by lipopolysaccharide (LPS) in peripheral blood mononuclear cells (PBMCs) is still not known. The objective of this study was to examine the impact of malvidin on inflammatory responses and oxidative stress in PBMCs as caused by LPS. The present findings showed that LPS significantly increased the expression of IL‐6, TNF‐α, IL‐1β, and COX‐2 mRNA and protein release from PBMCs 22 hr after treatments. It was also revealed that increased levels in cytokine expression coincided with increased phosphorylation of JNK, P65‐NF‐κB, and IKKα/IKKβ. Also, the expression of IL‐6, TNF‐α, IL‐1β, and COX‐2 mRNA induced by LPS as well as secretion of protein in PBMC has been significantly decreased by pretreatment of malvidin. Importantly, pretreatment of the cells with malvidin completely abrogated the phosphorylation of P65‐NF‐κB, JNK, and IKKα/IKKβ in LPS treated cells. Malvidin protection against LPS‐induced inflammation was coupled with a decline in the levels of nitric oxide metabolite and malondialdehyde, along with an increase in the ferric reducing antioxidant power, total thiol activity, and also superoxide dismutase and glutathione peroxidase activity. In accordance with this finding, malvidin may represent a promising therapeutic agent for the prevention of inflammation in PBMCs.