Biological methanation is a promising option for CO2 utilization and energy storage. While the underground condition is not appropriate for a methanation reaction, microorganisms act as a catalyst and make the reaction possible. This study investigates the performance of biological methanation in depleted gas reservoirs using numerical simulation. To do this, a one-dimensional synthetic homogeneous depleted gas reservoir is modeled with the two-phase flow comprising components H2, CO2, CH4, and H2O. Then, the simultaneous injection of CO2 and H2 into the reservoir is numerically simulated to evaluate the methane production rate in MATLAB Reservoir Simulation Toolbox (MRST) open-source software. Long-term results show propagating composition waves and pressure profiles. Sensitivity analysis reveals that methane production is positively correlated with the initial reservoir pressure and the number of methanogenic microorganisms, but negatively correlated with the temperature and the bacterial decay rate. The bacterial growth rate has an insignificant effect on methane production in this model. The bacterial population is the most critical parameter, as 1e7 methanogenic microorganisms per cubic meter of aqueous phase can produce 96% pure methane after 12 years. Overall, the work demonstrates harnessing in-situ bio-reactions to utilize CO2 and recover depleted gas reservoirs.