Putative alkaline hydrothermal systems on Noachian Mars were potentially habitable environments for microorganisms. However, the types of reactions that could have fueled microbial life in such systems and the amount of energy available from them have not been quantitatively constrained. In this study, we use thermodynamic modeling to calculate which catabolic reactions could have supported ancient life in a saponite-precipitating hydrothermal vent system in the Eridania basin on Mars. To further evaluate what this could mean for microbial life, we evaluated the energy potential of an analog site in Iceland, the Strytan Hydrothermal Field. Results show that, of the 84 relevant redox reactions that were considered, the highest energy-yielding reactions in the Eridania hydrothermal system were dominated by methane formation. By contrast, Gibbs energy calculations carried out for Strytan indicate that the most energetically favorable reactions are CO2 and O2 reduction coupled to H2 oxidation. In particular, our calculations indicate that an ancient hydrothermal system within the Eridania basin could have been a habitable environment for methanogens using NH4+ as an electron acceptor. Differences in Gibbs energies between the two systems were largely determined by oxygen—its presence on Earth and absence on Mars. However, Strytan can serve as a useful analog for Eridania when studying methane-producing reactions that do not involve O2.