The nutritive value and in vitro digestibility using the digestive enzyme extracts from different stages of silkworm larvae (Bombyx mori) were evaluated in different leaf positions (1, 2, 3, 4, or 5) of mulberry leaves (Morus spp.) with or without gamma irradiation treatment (native vs. irradiated). At least one of studied factors and their interaction had effects on the overall proximate composition and physicochemical properties (p < 0.05), in terms of water absorption index, water solubility, swelling power, pH, relative crystallinity, and FT-IR spectra. Cellulase activity was significantly decreased with larval stage, while a similar pattern was observed for amylase activity, but with relatively low activity in the first stage. The highest trypsin activity was observed in the fourth stage, followed by the second and fifth stages. These changes across the five larval stages could have significant effects on the in vitro digestibility of protein (IVPD) and carbohydrate (IVCD), as well as the effect of leaf position on IVCD. However, significant improvements in IVPD and IVCD were obtained for irradiated leaves relative to the control native leaves, independent of all studied factors.