Environmental pollution by the nearly nonbiodegradable polyethylene (PE) plastics is of major concern; thus, organisms capable of biodegrading PE are required. The larvae of the Greater Wax Moth, Galleria mellonella (Gm), were identified as a potential candidate to digest PE. In this study, we tested whether PE was metabolized by Gm larvae and could be found in their tissues. We examined the implication of the larval gut microbiota by using conventional and axenic reared insects. First, our study showed that neither beeswax nor LDPE alone favor the growth of young larvae. We then used Fourier transform infrared microspectroscopy (μFTIR) to detect deuterium in larvae fed with isotopically labeled food. Deuterated molecules were found in tissues of larvae fed with deuterium labeled oil for 24 and 72 h, proving that μFTIR can detect metabolization of 1 to 2 mg of deuterated food. Then, Gm larvae were fed with deuterated PE (821 kDa). No bioassimilation was detected in the tissues of larvae that had ingested 1 to 5 mg of deuterated PE in 72 h or in 19 days, but micrometer sized PE particles were found in the larval digestive tract cavities. We evidenced weak biodegradation of 641 kDa PE films in contact for 24 h with the dissected gut of conventional larvae and in the PED4 particles from excreted larval frass. Our study confirms that Gm larvae can biodegrade HDPE but cannot necessarily metabolize it.