Oxidative stress and inflammation are known to be linked to the development of chronic inflammatory conditions, such as type 2 diabetes and cardiovascular disease. Dietary polyphenols have been demonstrated to contain potent bioactivity against specific inflammatory pathways. Rice bran (RB), a by-product generated during the rice milling process, is normally used in animal feed or discarded due to its rancidity. However, RB is known to be abundant in bioactive polyphenols including phenolic acids. This study investigates the antioxidant and anti-inflammatory effects of RB phenolic extracts (25, 50, 100, and 250 µg/mL) on RAW264.7 mouse macrophage cells stimulated with hydrogen peroxide and lipopolysaccharide. Biomarkers of oxidative stress and inflammation such as malondialdehyde (MDA), intracellular reactive oxygen species, nitric oxide and pro-inflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-12, p70 (IL-12p70), and interferon-γ (IFN-γ) were measured in vitro. Treatment with RB extracts significantly decreased the production of MDA, intracellular reactive oxygen species, nitric oxide and pro-inflammatory cytokines (IL-6, IL-12p70, and IFN-γ) when compared to the control. It is proposed that RB phenolic extracts, via their metal chelating properties and free radical scavenging activity, target pathways of oxidative stress and inflammation resulting in the alleviation of vascular inflammatory mediators.