This study relates to developing future alternative fuels and focuses on the effects of a fuel’s molecular structure on its properties and performance in advanced propulsion systems. The tribological performance of various biomass-derived oxygenated alternative fuels, including butanol, pentanol, cyclopentanol, cyclopentanone, and gasoline and their blends with diesel, was investigated. Lubricity tests were conducted using a high-frequency reciprocating rig (HFRR). Cyclopentanone-diesel and cyclopentanol-diesel blends result in smaller wear scar sizes compared to using their neat forms. A lower steel disc contaminated with the alternative fuels during the HFRR tests resulted in worn surface roughness values lower than those of the neat diesel by up to 20%. It is believed that these reductions are mainly due to the presence of the hydroxyl group and the carbonyl group in alcohols and ketones, respectively, which make them more polar and consequently helps the formation of the protective lubrication film on the worn moving surfaces during the sliding process. Overall, the results from this study indicate that environmentally friendly cyclopentanol and cyclopentanone are practical and efficient fuel candidates for future advanced propulsion systems.