This work investigated the efficiency of Fenton oxidation with respect to the removal of chemical oxygen demand (COD), total organic carbon (TOC), and phenol in the treatment of heavily loaded pistachio processing industrial wastewater (PPIW). The study was implemented at lab scale and examined the impact of a range of key process parameters on overall performance including the initial Fe2+ concentration, the hydrogen peroxide (H2O2) concentration, the PPIW pH, and the reaction time. The results revealed that the optimum conditions for Fenton oxidation on PPIW were 1.32 g L-1 Fe2+, 19.2 g L-1 H2O2, pH = 3, and reaction time of 30 min. Given the optimal conditions, the removal efficiency of TOC, COD and phenol was 52.9%, 76.8%, and 85.3%, respectively. After optimization of the key process parameters, the Fenton process can be efficient in treating PPIW. This study confirms the hypothesis that Fenton oxidation can generally be effective in the treatment of wastewaters with high organic concentration either per se or as a pretreatment step within a larger conventional treatment scheme.