The growing demand for sustainable protein sources has increased interest in edible insects and their potential role within circular bioeconomy strategies. This study evaluated the suitability of brewer’s spent grain (BSG), cocoa bean shell (CBS), and banana peel (BP)
as alternative substrates for Tenebrio molitor rearing and assessed the valorization of the resulting biomass through pilot-scale supercritical CO2 extraction (CO2-SFE). Larvae reared on BSG-based and BP-based diets achieved growth performances comparable to those obtained with a conventional wheat bran diet, whereas CBS-based diet resulted in lower weight gain and feed intake. No significant differences in feed conversion ratio were observed among diets. Substrate composition also affected biomass nutritional quality, with larvae reared on the BSG-based diet exhibiting the highest protein content (60.4%), whereas larvae reared on CBS-based diet exhibited the highest lipid content (29.3%). CO2-SFE generated protein-enriched meals and lipid-rich extracts, yielding 12.9–15.4% oil depending on the substrate. Following extraction, protein content increased to 68.5%, 50.3%, and 60.2% in BSG-, CBS-, and BP-derived meals, respectively. The extracted oils were characterized by high levels of unsaturated fatty acids, with oleic acid (42.4–47.6%) as the predominant component. Overall, the results demonstrate that agro-industrial byproducts can be effectively converted into valuable insect-derived ingredients and highlight the potential of integrating substrate selection with green extraction technologies within insect biorefinery systems.