This study was performed to investigate the distribution of phenolic compounds in the peanut skins of various cultivars, as well as their antioxidant and anti‐inflammatory effect (Arachishypogaea L. cv. K‐Ol, cv. Sinpalkwang, cv. Daan, cv. Heuksaeng) and extraction solvent. The major components of red peanut cultivars (K‐Ol, Sinpalkwang, and Daan) were identified as proanthocyanidin, catechin, gallic acid, coumaric acid, and hesperidine, whereas the major components of black peanut cultivar (Heuksaeng) were identified as anthocyanin, ferulic acid, and quercetin. The DPPH and ABTS radical scavenging activities, and FRAP values were the highest in Daan followed by Sinpalkwng, K‐Ol, and Heuksang. Furthermore, the skin extracts of red peanuts effectively improved cell viability, reactive oxygen species generation, MDA concentration, and antioxidant enzyme activity (GR, GPx, CAT, and superoxide dismutase) in oxidative stress‐induced HepG2 cells, and reduced the expression of pro‐inflammatory factors (NO, TNF‐α, IL‐6, and IL‐1β) in LPS‐stimulated RAW 264.7 macrophages. These results suggest that red peanut skin extracts could effectively mediate physiological activity and provide valuable information for the use of peanut byproducts as functional food materials.