To clarify the effects of dietary inflammatory and pro-oxidative potential, we investigated the impact of the Dietary Inflammation Index (DII) and the Dietary Oxidative Balance Score (DOBS) on all-cause and disease-specific mortality. For DII and DOBS, 17,550 and 24,527 participants were included. Twenty-six and seventeen dietary factors were selected for scoring. Cox proportional hazards regression models were used. DII and DOBS were significantly associated with all-cause, CVD, and cancer mortality in this nationally representative sample of American adults. Compared with the lowest DII, the multivariable-adjusted hazard ratios (95% CI) of all-cause, CVD, and cancer mortality for the highest were 1.49 (1.23–1.80), 1.58 (1.08–2.33), and 1.56 (1.07–2.25). The highest quartile of DOBS was associated with the risk of all-cause death (HR 0.71, 95% CI 0.59–0.86). Pro-inflammatory and pro-oxidative diets were associated with increased risk for all-cause (HR 1.59, 95% CI 1.28–1.97), and CVD (HR 2.29, 95% CI 1.33–3.94) death compared to anti-inflammatory and antioxidant diets. Similar results were observed among the stratification analyses. Inflammation-reducing and oxidative-balancing diets are linked to lower all-cause and CVD mortality. Diets impact health by regulating inflammation and oxidative stress.