Natural gas injection (i.e., recycling) is a commonly used for enhanced oil recovery method and is potentially costeffective and efficient. However, natural gas injection, particularly methane, often has a high minimum miscibility pressure (MMP) which likely exceeds the fracture pressure of many otherwise viable reservoirs. Therefore, this work aims to investigate the potential of chemical-assisted MMP reduction of the methane-oil system to expand the application of miscible natural gas injection to more candidate reservoirs. In this context, we performed a study to test six potential surfactant-like chemicals with different polar headgroups (i.e., morpholine, aromatic sulfonic acid, aromatic carboxylic acid, and 2-oxypyrrolidine). The intent is to reduce the methane-oil interfacial tension using the vanishing interfacial tension method at a constant temperature of 373 K. First, at a concentration of 2 wt %, we tested the effect of the polar headgroups with the same hydrocarbon chain. Then, we investigated the effect of increasing the hydrocarbon chain length on the methane-oil miscibility. Our results show that chemical additives with the 2oxopyrrolidine and aromatic sulfonic acid functional groups give higher MMP reductions (8.7−9.6%, respectively) compared with aromatic carboxylic acid and morpholine groups, which only give limited or no MMP reduction. Moreover, the results show that the reduction in first contact miscibility pressure is higher (12.8−19.1%) compared to MMP. Furthermore, increasing the hydrocarbon chain length (from 10 to 13) of the 2-oxopyrrolidine and aromatic sulfonic acid molecules seems to decrease the efficiency in reducing MMP. Our results screen the potential of a combinatorial chemistry approach (where two molecules with differing sizes and functional groups can be readily joined together to make a large library of compounds) that can be used to identify chemical additives for reducing MMP of methane-oil. This approach underscores the importance of optimizing the functional group and hydrocarbon chain length in potential chemicals for MMP reduction. The outlined research results likely expand the application of miscible natural gas injection to deep and/or high-temperature reservoirs, in addition to the environmental benefits of reducing gas flaring and greenhouse gas emissions through natural-gas recycling.