<p>The superior lubrication performance and biodegradability of vegetable oil make it a promising alternative to traditional mineral oils as an eco-friendly lubricant. However, the limited antioxidant properties and poor extreme pressure resistance of the vegetable oils restrict their use in high-temperature and high-pressure environments. Epoxidation-isomerization chemical modification addresses these challenges by eliminating the double bonds in fatty acids and introducing polar groups/side chains in the vegetable oils. However, the ambiguity in the principles of lubricant performance improvement and grinding performance evaluation due to differences in reactivity of materials tends to limit the advancement of lubricant technology. To address this research gap, ten lubricants with varying carbon chain lengths and degrees of isomerization were synthesized in an epoxidation-isomerization reaction. The resultant product’s structures were then verified, and their lubrication properties were tested. This article first characterizes the structural and functional properties of the rapeseed vegetable oil using Fourier transform infrared (FTIR) spectroscopy. Secondly, the mechanism for enhancing the viscosity and tribological properties of modified lubricants was analyzed based on differences in the molecular structure of each of the produced lubricants. Finally, four distinct grinding conditions were applied to verify the feasibility of modified lubricant in minimum quality lubrication (MQL) machining. The results indicate that the viscosity of the epoxidized-isomerized rapeseed oil decreased as the side chain lengths and degree of isomerization increased. The maximum non-card bite load is significantly higher than that of pure rapeseed oil, and it decreases with an increase in the length of the added side chain. The friction coefficient of epoxidized-isomerized rapeseed oil decreases significantly compared to unmodified rapeseed oil. The friction coefficient of epoxidized-isomerized heptyl ester decreases by approximately 44.1% and 40.8% under loads of 147 N and 392 N, respectively. Furthermore, epoxidized heptyl ester and epoxidized octyl ester are chosen as lubricants for grinding experiments on nickel-based alloy 718. Compared with pure rapeseed oil, the heptanoic ester MQL reduced normal and tangential grinding force by about 11.54% and 9.90%, respectively. The surface roughness parameters <i>Sa</i> and <i>Sq</i> decreased by approximately 29.79% and 28.11%, respectively. The incorporation of Al₂O₃ nanoparticles in the oils was found to further improve the grinding performance. These topics discussed could offer some important insights on researchers and engineers in the fields of interface lubrication and precision machining.</p>