Black soldier fly larvae (BSFL) are gaining importance in animal feeding due to their ability to upcycle low-value agroindustry by-products into high-protein biomass. The present study evaluated the nutritional composition of BSFL reared on brewer's by-product (BBP) and the impact of thermal (90 °C for 10/15 min) and high-pressure processing (HPP; 400/600MPa for 1.5/10 min) treatments on the microbial levels and digestibility in both ruminant and monogastric models. BBP-reared BSFL contained a high level of protein, amino acids, lauric acid, and calcium, and high counts of total viable counts (TVC; 7.97), Enterobacteriaceae (7.65), lactic acid bacteria (LAB; 6.50), and yeasts and moulds (YM; 5.07). Thermal processing was more effective ( < 0.05) than any of the HPP treatments in reducing TVC. Both temperature of 90 °C and pressure of 600 MPa reduced the levels of Enterobacteriaceae, LAB, and YM below the detection limit. In contrast, the application of the 400 MPa showed a reduced inactivation ( < 0.05) potential. Heat-treated samples did not result in any significant changes ( > 0.05) on any of the digestibility models, whereas HPP showed increased and decreased ruminal and monogastric digestibility, respectively. HPP did not seem to be a suitable, cost-effective method as an alternative to heat-processing for the large-scale treatment of BSFL.