Background: Pistachio, with the scientific name Pistacia vera L., a native plant in Asia, is a member of the Anacardiaceae family. Pistachio nuts and skins are known as a rich source of phenolic compounds with antioxidant, anti-inflammatory, and antimicrobial properties. Objectives: In the current study, the industrial production of phenolic compounds with antioxidant activity was investigated because of the high mass production of pistachio skin in Iran. Methods: The extraction of two pistachio cultivars, namely Kalleghuchi and Ohadi were carried out by using two methods (maceration and ultrasonic extraction) and four solvents (acetone 70%, ethanol 50%, methanol 50%, and water). Antioxidant properties of pistachio skins were determined by three methods (Folin-Ciocalteau colorimetric method, DPPH assay, TLC/DPPH analysis). Results: The results showed that the highest content of total phenolic compounds were measured by ultrasonic and maceration methods related to Ohadi and Kallehghuchi in acetone solvents 17.4 ± 0.04 and 17.26 ± 0.1 mg/g DW, respectively. The highest antioxidant activity was measured by ultrasonic and maceration methods related to Ohadi in acetone and water solvents IC50 = 0.057 ± 0.001 and 0.059 ± 0.002 µg/ml, respectively. By TLC/DPPH analysis, gallic acid, 4-hydroxy-3, 5-dimethoxy benzoic acid, tannic acid, and some unidentified compounds were determined. By HPLC analysis, gallic acid, coumaric acid, cinnamic acid, 4-hydroxy-cinnamic acid, and 4-hydroxy benzoic acid were determined. Conclusions: In conclusion, this study clarifies some special biochemical characteristics of pistachio skins. Therefore, according to the results of the study, pistachio skins could be successfully used in the food and pharmaceutical industries.