Sufficient quantity of trace metals is essential for a well performing anaerobic digestion (AD) process. Among the essential trace elements in active sites of multiple important enzymes for AD are iron and nickel ions. In the present study, iron and nickel in the form of Fe2O3 and NiO were coated on TiO2 nanoparticles to be used in batch and continuous operation mode. The effect of TiO2, Fe2O3–TiO2, and NiO–TiO2 nanoparticles on each step of AD process was assessed utilizing simple substrates (i.e. cellulose, glucose, acetic acid, and mixture of H2–CO2) as well as complex ones (i.e. municipal biopulp). The hydrolysis rate of cellulose substrate increased with higher dosages of the coated TiO2 with both metals. For instance, the hydrolysis rate was increased up to 54% at Fe2O3–TiO2 and at a concentration of 23.5 mg/L for NiO–TiO2 it was increased up to 58%, while higher dosage suppressed the hydrolytic activity. Experimental results revealed that low dosages of NiO–TiO2 increased the accumulated methane production up to 24% probably by increasing the enzymatic activity of acetoclastic methanogenesis. NiO–TiO2 showed positive effect on batch and continuous AD of biopulp and improved methane yield up to 8%.