Red pepper spice (RP) and turmeric (TM) are used as flavorings in foods and for medicinal purposes. Utilizing a randomized, doubled-blinded, placebo-controlled, crossover design (2-week washout), 4-week supplementation with RP (1 g/d) or TM (2.8 g/d) was tested for influences on inflammation and oxidative stress in 62 overweight/obese (body mass index ≥ 27 kg/m²) females (40-75 years) with systemic inflammation (C-reactive protein, CRP ≥ 2 mg/l). Overnight, fasted blood samples were collected pre- and post-supplementation, and analyzed for oxidative stress (F₂-isoprostanes, oxidized low density lipoprotein), inflammation (CRP and seven inflammatory cytokines), and metabolic profiles using gas chromatography-mass spectrometry with multivariate partial least square discriminant analysis (PLS-DA). Pre- to post-supplementation measures of inflammation and oxidative stress for both RP and TM did not differ when compared to placebo (all interaction effects, P > 0.05), and global metabolic difference scores calculated through PLS-DA were non-significant (both spices, Q²Y < 0.40). These data indicate that 4-week supplementation with RP or TM at culinary levels does not alter oxidative stress or inflammation in overweight/obese females with systemic inflammation, or cause a significant shift in the global metabolic profile.