This report describes the asymmetric synthesis of a focused library of enantiopure structured tri-acylglycerols (TAGs) comprised of a single saturated fatty acid (C6, C8, C10, C12, C14 or C16), a pure bioactive n-3 polyunsaturated fatty acid (EPA or DHA) and a potent drug (ibuprofen or naproxen) intended as a novel type of prodrugs. One of the terminal sn-1 or sn-3 positions of the glycerol backbone is occupyed with a saturated fatty, the remaining one with a PUFA, and the drug entity is present in the sn-2 position. This was accomplished by a six-step chemoenzymatic approach starting from enantiopure (R)- and (S)-solketals. The highly regioselective immobilized Candida antarctica lipase (CAL-B) played a crucial role in the regiocontrol of the synthesis. All combinations, the total of 48 such prodrug TAGs were prepared, isolated and fully characterized, along with 60 acylglycerol intermediates, obtained in very high to excellent yields.