The role of Maillard reaction products (MRPs) in anaerobic digestion of the waste activated sludge (WAS) is frequently neglected. This study aimed to investigate the inhibition effect of MRPs on the anaerobic digestion of WAS under alkaline-thermal pretreatment, particularly focusing on the effects of different thermal-treatment temperatures, substrate sources, and the presence of humic acids. The results revealed that the thermaltreatment temperature played a critical role in the generation of MRPs. More refractory MRPs were generated at higher temperatures (>= 130 degrees C), which resulted in a decrease in methane production ranging from 16.53 % to 23.11 %. Molecular docking analysis indicated that the MRPs generated from different amino acid substrates contained distinct components, including furans, pyrroles, and pyrazines, which were identified as typical refractory products. Furthermore, the inherent content of HA in WAS had no significant effect on methane production. Metagenomic analysis demonstrated a reduction in the relative abundance of Bacteroidota from 10.20 % (control) to 8.13 % (MRPs-160 degrees C), contributing to the influence of MRPs on the acidogenesis by disrupting the hydrolytic and fermentative activities associated with this microbial phylum. The gene expression of enzymes classified under Enzyme Commission (EC) numbers 1.8.7.3 and 1.8.98.4 was primarily inhibited in the presence of MRPs, significantly correlating with central metabolism and methane metabolism. As a result, the acetogenesis and methanogenesis in the microorganisms were affected, leading to an inhibition of anaerobic digestion. This study provides novel insights into the specific inhibitory effects of MRPs on methanogenic activity during anaerobic digestion, contributing to the mitigation of the Maillard reaction and the improvement of anaerobic digestion efficiency.