While it is recognised that humans are constantly exposed to plastics, there are limitations in understanding the extent of this exposure, particularly dietary exposure. This lack of information is partly due to challenges with the analysis of complicated matrices. This study aimed to assess the impact of medium to high lipid content (> 3%) food samples on the accurate quantification of polyethylene (PE), using pyrolysis-gas chromatography mass spectrometry, and develop an alternative sample processing strategy. Analysis of saturated, monounsaturated and polyunsaturated fats was demonstrated to form the same pyrolysis products as PE, producing a significant interference hindering quantification. An extraction protocol was developed that involves enzyme digestion to break the lipids into smaller chain fatty acids, removal of these interferences with pressurised liquid extraction washes, before a final extraction of the PE by pressurised liquid extraction. This new method was validated through the analysis of three medium- to high-fat content foods: cow’s milk, eggs and lamb meat, where PE recoveries were acceptable (104% to 127%). Method detection limits were also significantly reduced from 1.9 to 0.05 µg/injection (380 to 10 µg/g) with the new protocol, through the removal of matrix background. PE traces were observed in the three food matrices of 72-240 µg/g, significantly reduced as compared to samples extracted with the old method where concentrations of 12-32 mg/g were calculated, demonstrating the potential for overestimation of dietary exposure. Finally, a simple protocol is reported for future studies to (i) determine if an interference is present and (ii) sample processing methods to remove identified interferences