Simple Summary: Alfa-lipoic acid (ALA) is an important antioxidant that could be added to animal feed as a nutritional supplement. To improve its stability in the digestive system, ALA was encapsulated in chitosan nanoparticles. The nanoparticles containing ALA were stable in stomach-like conditions and were able to cross the intestinal barrier. Chitosan-based nanoparticles seem to be an attractive administration method for antioxidants, or other sensible additives, in food. The addition of the antioxidant α-lipoic acid (ALA) to a balanced diet might be crucial for the prevention of comorbidities such as cardiovascular diseases, diabetes, and obesity. Due to its low half-life and instability under stomach-like conditions, α-lipoic acid was encapsulated into chitosan nanoparticles (Ch-NPs). The resulting chitosan nanoparticles containing 20% w/w ALA (Ch-ALA-NPs) with an average diameter of 44 nm demonstrated antioxidant activity and stability under stomach-like conditions for up to 3 h. Furthermore, fluorescent Ch-ALA-NPs were effectively internalized into 3T3-L1 fibroblasts and were able to cross the intestinal barrier, as evidenced by everted intestine in vitro experiments. Thus, chitosan-based nanoparticles seem to be an attractive administration method for antioxidants, or other sensible additives, in food. [ABSTRACT FROM AUTHOR]