There is an increasing need to address the potential risks arising from combined exposures to multiple residues from pesticides in the diet. Pesticide residue‐related pollution is a problem that arises because of the increased use of pesticides in agriculture to meet the growing demands of food production. In this study, pesticide residue data were obtained based on an optimized extraction method. For this purpose, we established a method based on quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction for simultaneous determination of imidacloprid (IMI) and acetamiprid (ACT) in pistachio nuts. The parameters influencing the QuEChERS method were the sample‐to‐water ratio and adsorbent amounts. As a result, both were optimized to improve the recovery of the analytes as well as the clean‐up efficiency of the pistachio matrix. Our results indicated that a freeze‐out step and use of primary and secondary amines as an adsorbent led to much cleaner chromatograms with lower baseline drift, without using graphitized carbon black and C18‐based adsorbent, which reduced both cost and time of analysis. Following extraction, the pesticide residues were separated and quantified by reverse‐phase HPLC. For validation purposes, recovery studies were carried out using a concentration range from 20 to 2500 μg/L at nine levels. The suitable linearity, precision, and accuracy were obtained with HPLC–UV with recoveries of 70.37%–89.80% for IMI and 81.05%–113.57% for ACT, with relative standard deviations <12%. The validated method was successfully applied to the analysis of pistachio samples collected from a field trial to estimate maximum residue limits. There was no significant health risk for consumers via pistachio consumption.