Plastic waste pollution poses a global ecological challenge¹, and plastic breakdown through biological systems such as insects and their enzymes could be a future solution for plastic waste recycling. The larvae of the Greater Wax moth, Galleria mellonella (Gm), mealworm (Tenebrio molitor) and black soldier fly (Hermetia illucens) have shown their potential to degrade nonbiodegradable polyethene (PE)²; however, the underlying biochemical mechanism the larvae used to survive and degrade plastic waste remains unknown. Here, we fed the insect larvae with six types of plastics for one week and dissected the larvae to separate body and gut samples for Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS)-based proteomics experiments. We have found that the larvae responded to each plastic type differently, and detected bioactive peptides from the insects associated with the larval nutrient stress management mechanism. Most notably, the larvae fed with the pink-coloured expanded low-density polyethene foam block markedly improved physiological responses with significant changes in enzyme categories such as hydrolases and oxidoreductases. Network analysis revealed that the plastic diet impacts the wax moth body proteome; proteins involved in triglyceride breakdown, lipid metabolism, storage and energy production markedly increased within the polystyrene-fed larvae, and the muscle-building proteins were increased in the polyester fibre and polystyrene-fed larvae. Our results demonstrate that the wax moth and mealworm larvae could be investigated further to characterise enzymes from the insect and the microbial communities’ presence in their gut to design plastic-degrading enzymes at the industrial scale.