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BACKGROUND In recent years, the design of food-grade Pickering emulsion delivery systems has become an effective strategy for improving the low bioavailability of bioactive substances. Protein-based Pickering emulsions have received extensive attention due to the high biocompatibility and loading capacity. The bioavailability of active substances is mainly evaluated by simulating in vitro gastrointestinal digestion. As a model organism for antioxidation and antiaging, Caenorhabditis elegans (C. elegans) can provide additional biological information for the in vivo utilization of active substances. RESULTS After the introduction of caffeic acid, the average particle size and Zeta potential of the casein-caffeic acid complex nanoparticles (CCP) were 171.11 nm and - 37.73 mV, respectively. The three-phase contact angle was also increased to 89.8°. By using CCP to stabilize Pickering emulsion (CCE), the retention quantity of the embedded curcumin increased by 2.19 times after 28 days. In the simulated gastric digestion, curcumin degradation in CCE was reduced by 61.84%, released slowly in the intestinal environment, and the final bioaccessibility was increased by 1.90 times. In C. elegans, CCE significantly reduced ROS accumulation, increased SOD activity by 2.01 times and CAT activity by 2.30 times, decreased MDA content by 36.76%, prolonging the lifespan of nematodes by 13.33% under H2 O2 stimulation and improving bioavailability in vivo. CONCLUSION The results illustrated that CCP-stabilized Pickering emulsion can efficiently implement the physiological activities of bioactive compounds in vitro digestion and C. elegans, and thus, it can be regarded as a reliable delivery system for food and medicine. This article is protected by copyright. All rights reserved.