Frequent consumption of nuts has been linked to a lowered risk of cardiovascular disease. Phytochemicals, especially phenolics, in nuts may be considered to be the major bioactive compounds for health benefits. Nine types of tree nuts and peanuts commonly available in the United States were evaluated for total phenolic and flavonoid contents, antioxidant, and antiproliferative activities. The profiles of total phenolics and flavonoids, including both soluble free and bound forms, were investigated by utilizing solvent extraction, base digestion, and solid-phase extraction methods. Walnuts had the highest total phenolic and flavonoid contents (1580.5 ± 58.0 mg/100 g, 744.8 ± 93.3 mg/100 g, respectively). Walnuts also possessed the highest total antioxidant activity (458.1 ± 14.0 μmol of vitamin C equiv/g of nut). Both soluble phenolic and flavonoid contents were positively correlated with total antioxidant activity (R2 = 0.9901, p