Aquatic products are considered a potential source of novel bioactive proteins, which are used as therapeutic drugs for the treatment of different diseases (such as oxidative stress, immunocompromised, and inflammation), as well as nutraceuticals and cosmetics. However, the physical and chemical properties of proteins are unstable, and they are easily denatured by the influence of external high temperature and polar pH during processing, resulting in the loss of their functional activity. Herein, Fenneropenaeus chinensis water-soluble protein (FCWP) and Lateolabrax japonicus water-soluble protein (LJWP) were encapsulated within spherical biopolymer microgels composed of pectin and chitosan produced by the microfluidic device. The encapsulated samples remained inside the microgels when they were exposed to upper gastrointestinal but were released when they were exposed to simulated colonic fluid due to the hydrolysis effect by enzymes secreted by the colonic microflora. The results showed that microgels improve the thermal stability of FCWP and LJWP due to the interaction between polysaccharides and proteins in the microgels. In addition, microgels encapsulation did not affect the antioxidant and immunoenhancing activities of FCWP and LJWP. In summary, these microgels are suitable for oral colon-specific delivery in functional foods and supplements.