In this study, leather fleshing waste (LFW) and a complementary substrate (food waste leachate; FWL) were co-digested. The main focus of research was to study effects on biogas production caused by interactions between co-substrates when combined in different mixing ratios and changes on microbial community structures. Due to a positive effect of co-digestion (i.e., establishing nutrient equilibrium), the adjusted substrates for optimum C/N ratio by blending LFW and FWL resulted in significantly higher biodegradability and biomethane production (375.5-520.8 mL CH4 g-1 VS) than the mono-digestion of each substrate. According to co-digestion of LFW and FWL, microbial communities became more diverse and the changes of microbial structure influenced the biomethane production performance. Among the co-digesting conditions, the biomethane production yield and rate of the samples were in reverse order and the results were firmly associated with the relative richness of lipids (yield-related) and proteins (rate-related) in the co-substrates.