In this study, we evaluate the usefulness of mature landfill leachate (MLL) as a carrier allowing hydrodynamic cavitation (HD) of brewery spent grain (BSG). The HD experiments were conducted using an orifice plate with a conical concentric hole of 3/10 mm (inlet/outlet diameter) as a constriction in the cavitation device. The initial pressure was 7 bar and the number of recirculation passes through the cavitation zone reached 30. The results showed that complex organic matter was degraded and solubilized when cavitating the MLL and BSG mixture. The biochemical oxygen demand (BOD5) increased by 45% and the BOD5/total chemical oxygen demand (COD) ratio increased by 69%, whereas the COD, total solids, and nutrient concentration dropped noticeably. However, Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) revealed the generation of possibly toxic HD byproducts such as aromatic compounds. This seems to indicate that MLL could not be regarded as a suitable carrier for BSG cavitation.