Abstract: The present study aimed to utilize extracellular vesicles (EVs) derived from Lactobacillus paracasei as delivery carriers to construct an astaxanthin (AST)-encapsulated system (AST@EVs), thereby improving the water solubility, stability, and bioavailability of AST. The research methods included the isolation of EVs via differential centrifugation and ultracentrifugation. Systematic evaluations of the physicochemical properties, digestive stability, antioxidant activity, and anti-fatigue effect of AST@EVs were conducted using characterization analysis, in vitro simulated digestion, free radical scavenging assays, and the C2C12 cell model. The results demonstrated that EVs with a typical spherical structure and an average particle size of 85.97 nm were successfully prepared. After optimizing the encapsulation ratio (2:1), the encapsulation efficiency and protein loading capacity of AST@EVs reached 84.94% and 12.74%, respectively, with the particle size increasing to 109.37 nm. Additionally, Fourier transform infrared spectroscopy (FTIR) and electron microscopy results confirmed the effective encapsulation of AST in EVs. In in vitro digestion, the retention rate of AST in AST@EVs was significantly higher than that in the free AST group and the physical mixture group. The scavenging rates of AST@EVs against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical (ABTS⁺) were 83.92% and 62.81%, respectively, indicating a significant enhancement in antioxidant capacity. Cellular experiments showed that AST@EVs could promote the uptake of AST by C2C12 cells (reaching 5.27 μg/mL), alleviate oxidative stress, regulate the activities of superoxide dismutase (SOD) and catalase (CAT), and reduce the level of malondialdehyde (MDA). Meanwhile, AST@EVs inhibited the increase in lactate dehydrogenase (LDH) and creatine kinase (CK) activities, enhanced glycogen storage, and restored the activities of enzymes related to mitochondrial function. In conclusion, the EV-based encapsulation strategy can significantly enhance the stability, antioxidant capacity, and anti-fatigue efficacy of AST. This study provides a new idea for the development of functional foods and anti-fatigue drugs.