Anaerobic co-digestion generally results in a higher yield of biogas than mono-digestion, hence co-digestion has become a topic of general interest in recent studies of anaerobic digestion. Compared with mono-digestion, co-digestion utilizes multiple substrates. The balance of substrate nutrient in co-digestion comprises better adjustments of C/N ratio, pH, moisture, trace elements, and dilution of toxic substances. All of these changes could result in positive shifts in microbial community structure and function in the digestion processes and consequent augmentation of biogas production. Nevertheless, there have been few reviews on the interaction of nutrient and microbial community in co-digestions. The objective of this review is to investigate recent achievements and perspectives on the interaction of substrate nutrient balance and microbial community structure and function. This may provide valuable information on the optimization of combinations of substrates and prediction of bioreactor performance.