Astaxanthin (AST) has outstanding antioxidant and anti-inflammation bioactivities, but the low biocompatibility and stability limit its application in foods. In this study, N-succinyl-chitosan (NSC)-coated AST polyethylene glycol (PEG)-liposomes were constructed to enhance the biocompatibility, stability, and intestinal-targeted migration of AST. The AST NSC/PEG-liposomes were uniform in size, had larger particles, greater encapsulation efficiency, and better storage, pH, and temperature stability than the AST PEG-liposomes. AST NSC/PEG-liposomes exerted stronger antibacterial and antioxidant activities against Escherichia coli and Staphylococcus aureus than AST PEG-liposomes. The NSC coating not only protects AST PEG-liposomes from gastric acid but also prolongs the retention and sustained release of AST NSC/PEG-liposomes depending on the intestinal pH. Moreover, caco-2 cellular uptake studies showed that AST NSC/PEG-liposomes had higher cellular uptake efficiency than AST PEG-liposomes. And AST NSC/PEG-liposomes were taken up by caco-2 cells through clathrin mediated endocytic, macrophage pathways and paracellular transport pathway. These results further proved that AST NSC/PEG-liposomes delayed the release and promoted the intestinal absorption of AST. Hence, AST PEG-liposomes coated with NSC could potentially be used as an efficient delivery system for therapeutic AST.