•Side-stream thermophilic anaerobic digestion (STA) improved methane production performance.•STA activated organic matter conversion, key enzymes, and KEGG pathways.•STA concentrated active genera, enriched syntropic oxidizing bacteria and Methanosarcina.•STA enhanced acetoclastic methanogenesis and controls adverse effects of thermal stimulation. Anaerobic digestion (AD) is a favorable way to convert organic pollutants, such as food waste (FW), into clean energy through microbial action. This work adopted a side-stream thermophilic anaerobic digestion (STA) strategy to improve a digestive system's efficiency and stability. Results showed that the STA strategy brought higher methane production as well as higher system stability. It quickly adapted to thermal stimulation and increased the specific methane production from 359 mL CH4/g·VS to 439 mL CH4/g·VS, which was also higher than 317 mL CH4/g·VS from single-stage thermophilic anaerobic digestion. Further exploration of the mechanism of STA using metagenomic and metaproteomic analysis revealed enhanced activity of key enzymes. The main metabolic pathway was up-regulated, while the dominant bacteria were concentrated, and the multifunctional Methanosarcina was enriched. These results indicate that STA optimized organic metabolism patterns, comprehensively promoted methane production pathways, and formed various energy conservation mechanisms. Further, the system's limited heating avoided adverse effects from thermal stimulation, and activated enzyme activity and heat shock proteins through circulating slurries, which improved the metabolic process, showing great application potential. Display omitted