The present study aimed at isolating and elucidating the structure of the main components of Pistacia khinjuk L. and exploring its potential anti-inflammatory effect in different experimental models. The extract was evaluated for anti-inflammatory activity by measuring paw volume in three experimental models. Then, prostaglandin E2 (PGE2) level, ear edema, tissue myeloperoxidase (MPO) activity, histopathology, nitric oxide (NO) level, and tumor necrosis factor-α (TNF-α) level were assessed. Seven phenolic compounds, mainly flavonoids and galloylated compounds, were isolated from the aqueous methanol extract: gallic acid (1), methyl gallate (2), quercetin-3-O-β-d-4C1-galactopyranoside (hyperin) (3), myricetin-3-O-α-l-1C4-rhamnopyranoside (myricitrin) (4), 1,6-digalloyl-β-d-glucose (5), 1,4-digalloyl-β-d-glucopyranoside (6), and 2,3-di-O-galloyl-(α/β)-4C1-glucopyranose (nilocitin) (7). The anti-inflammatory activity was evidenced by decreased carrageenan-induced rat paw edema and PGE2 elevation. In the croton oil–induced ear edema model, MPO activity was significantly inhibited, and inflammatory histopathological changes were ameliorated. In the rat air pouch model, NO generation and TNF-α release were significantly inhibited. The isolation and nuclear magnetic resonance spectral data of compound 6 from the genus Pistacia are revealed for the first time. Also, P. khinjuk L. aqueous methanol extract possesses anti-inflammatory activity in several experimental models.