Food waste (FW) characterized by a low carbon/nitrogen (C/N) ratio ranging between 6 and 19 was used to investigate the feasibility and mechanism of maneuvering inoculum-to-substrate ratio (ISR) to alleviate the metabolic imbalance caused by imbalanced nutrients in the AD process, through biochemical methane potential tests and methanogenic pathway analysis. The maximum methane yield of 0.4 L/g of volatile solid (VS) was obtained at a C/N ratio of 11 and an ISR of 10:3. Increasing ISR from 1:2 to 10:3 promoted methane production by ∼20% via an enhancement in acetoclastic methanogenesis and the hydrolysis of carbohydrates and proteins. At lower ISR < 1, hydrogenotrophic methanogenic and syntrophic bacteria dominated, and methane production decreased by ∼ 20% due to the energy disadvantages of syntrophic methanogenesis. Efficient digestion of FW with low C/N ratio FW could be achieved by using metabolic pathways to regulate it and increasing ISR from 1:1 to 10:3.