Heparin is a widely used FDA-approved anticoagulant with a market size of approximately 5 trillion KRW. Among various types of heparin, low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), is widely utilized due to its enhanced anticoagulant efficacy, prolonged duration of action, and extended half-life. While the long-term effects of LMWH offer significant benefits for patients undergoing preventive therapy, achieving sustained activity remains a major challenge. In this study, we designed and evaluated a nanoengineered LMWH-octadecylamine conjugate (LMHO) that maintains approximately 97 ± 3% of LMWH activity through site-specific conjugation at the reducing end, ensuring prolonged anticoagulant action. LMHO self-assembles into nanoparticles with an average size of 127.1 ± 0.7 nm in aqueous solution without requiring an additional nanocarrier and binds to serum albumin, facilitating a lipid-based albumin-mediated shuttling effect. This conjugate can circulate in the bloodstream for 4–5 days. We validated the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative carrier-free polysaccharide delivery system, enhanced by nanoengineered albumin-mediated shuttling, presents a promising platform to overcome the limitations of conventional anticoagulant therapies.