Abstract: To address the inherent limitations of phosphatidylserine (PS) self-assembled cochleates, including poor structural stability, low assembly controllability, and a tendency for particle aggregation, this study proposes the use of alginate-g-oleylamine derivative (Alg-OA) as a coating regulator to construct an Alg-OA-coated PS cochleates composite delivery system (Alg-OA/PS-Cochleates), aiming to achieve efficient encapsulation and controlled release of the model protein drug lactoferrin (LF). First, the oleylamine-grafted alginate derivative (Alg-OA) was synthesized via carbodiimide chemistry, exhibiting a critical micelle concentration (CMC) of 0.108 mg/mL, a self-assembled micelle size of approximately 307.1 nm, and a zeta potential of −42.7 mV. Subsequently, PS-Cochleates were prepared using the trapping film method, and stable coating of Alg-OA on the cochleate surface was achieved through synergistic hydrophobic association and calcium ion crosslinking. Experimental results demonstrated that Alg-OA coating significantly reduced the Zeta potential for the LF loaded PS-Cochleates from −19.2 mV to −39.5 mV and decreased the polydispersity index (PDI) from 0.35 to 0.28, indicating markedly improved particle dispersibility and stability. Small-angle X-ray scattering (SAXS) characterization confirmed that the coating did not disrupt the multilayered ordered structure of the cochleates, with a lamellar repeat spacing of 5.1 nm. In terms of drug loading performance, Alg-OA/PS-Cochleates achieved the encapsulation efficiency (EE) of 65.6 ± 4.1% and drug loaded rate (LC) of 7.8 ± 0.3% for LF, which were significantly higher than that of uncoated PS-Cochleates (50.3 ± 3.6% and 6.2 ± 0.2%). In vitro release profiles exhibited pronounced pH-responsive behavior (release was hindered in simulated gastric fluid (SGF) but accelerated in simulated intestinal fluid (SIF)), along with sustained release characteristics lasting for nearly 60 h. Cytotoxicity assays revealed that the Alg-OA/PS-Cochleates maintained cell viability above 90% within the tested concentration range, indicating favorable biocompatibility. Furthermore, the particle size remained relatively stable after 4 weeks of storage at 4℃, demonstrating good long-term storage stability. The Alg-OA-coated cochleate delivery system effectively overcomes the key technical challenges of poor structural stability and particle aggregation in PS-Cochleates, exhibiting pH-responsive controlled release, excellent biocompatibility, and superior sustained-release performance, thus showing great potential in oral protein drug delivery applications.