Design of environmentally friendly lubricants derived from renewable resources is highly desirable for many practical applications. Here, Orychophragmus violaceus (Ov) seed oil is found to have superior lubrication properties, and this is based on the unusual structural features of the major lipid species-triacylglycerol (TAG) estolides. Ov TAG estolides contain two non-hydroxylated, glycerol-bound fatty acids (FAs) and one dihydroxylated FA with an estolide branch. Estolide branch chains vary in composition and length, leading to their thermal stability and functional properties. Using this concept, nature-guided estolides of castor oil were synthesized. As predicted, they showed improved lubrication properties similar to Ov seed oil. Our results demonstrate a structure-based design of novel lubricants inspired by natural materials.