Anaerobic digestion (AD) has been used widely as a form of energy recovery by biogas production from the organic fraction of municipal solid wastes (OFMSW). The aim of this study was to evaluate the effect of the introduction of co-substrates (restaurant wastes, corn whole stillage, effluents from the cleaning of chocolate transportation tanks) on the thermophilic anaerobic digestion process of the mechanically separated organic fraction of municipal solid wastes in a full-scale mechanical-biological treatment (MBT) plant. Based on the results, it can be seen that co-digestion might bring benefits and process efficiency improvement, compared to mono-substrate digestion. The 15% addition of effluents from the cleaning of chocolate transportation tanks resulted in an increase in biogas yield by 31.6%, followed by a 68.5 kWh electricity production possibility. The introduction of 10% corn stillage as the feedstock resulted in a biogas yield increase by 27.0%. The 5% addition of restaurant wastes contributed to a biogas yield increase by 21.8%. The introduction of additional raw materials, in fixed proportions in relation to the basic substrate, increases biogas yield compared to substrates with a lower content of organic matter. In regard to substrates with high organic loads, such as restaurant waste, it allows them to be digested. Therefore, determining the proportion of different feedstocks to achieve the highest efficiency with stability is necessary.