Abstract: To address the key problems of poor stability and low bioavailability of astaxanthin that limit its application, the effects of sodium caseinate (SC), sodium starch octenyl succinate (SOSS), and modified soy phospholipid (MSP) on the physicochemical characteristics, stability, and bioavailability of astaxanthin nanoemulsions were investigated, with the synthetic emulsifier Tween 80 used as a control, and the most appropriate emulsifiers were screened. Astaxanthin emulsions were prepared by high-pressure homogenization. The interfacial tension of each emulsifier was analyzed, and the particle size, zeta potential, viscosity, encapsulation efficiency, and macroscopic and microscopic structures of the emulsions were characterized. The stability was evaluated through high-speed centrifugation, high-temperature exposure, and long-term storage. Finally, the bioavailability characteristics were studied using an in vitro simulated digestion model. The results showed that SOSS exhibited an interfacial tension (14.33 mN/m) similar to that of Tween 80, compared with SC and MSP. The emulsion was observed to be light pink, with a smaller particle size (188.53 nm) and higher viscosity (22.19 mPa·s), properties conducive to emulsion stability. Moreover, emulsion droplets were found to be small and uniformly distributed without obvious aggregation, and encapsulation efficiency was determined to be higher than that of the Tween 80 emulsion. Additionally, the SOSS-stabilized emulsion demonstrated excellent centrifugal, thermal, and storage stability. No stratification or significant changes in particle size or potential were observed before and after centrifugation, with the lowest Ke values recorded. During high-temperature treatment, astaxanthin retention remained above 83%. Under storage at 25 ℃ and 4 ℃ for 28 days, the emulsion retained a homogeneous state without delamination or oil droplet precipitation, and astaxanthin retention rates were measured at 86.21% and 91.14%, respectively. Furthermore, in vitro digestion simulation revealed a high degree of lipid digestion, with bioavailability quantified at 33.65%, indicating enhanced absorption and utilization. Consequently, emulsions prepared with SOSS were confirmed to possess favorable physicochemical characteristics, stability, and bioavailability. A theoretical basis and technical guidance for astaxanthin application in food and medicine are provided by these findings.