This study investigates the impact of hydrophobic modification on the immunogenicity, cytotoxicity, and inflammatory response of Alaska pollock gelatin (ApGltn) microparticles (MPs). Gelatin, known for its inherent biocompatibility, was modified with decyl group (C10) to explore potential alterations in its interaction with the immune system. Immunogenicity was evaluated through the measurement of material-specific IgM and IgG responses, indicating no significant increase post-modification. Cytotoxicity against Caco-2 cell lines and NF-κB-mediated LPS-induced inflammation were also assessed, revealing no exacerbation by the modified MPs. Furthermore, C10 modification with different types of linkage such as secondary amine and amide structure did not influence immune reactivity. These findings suggest that C10 modification maintains the non-immunogenicity and biocompatibility of gelatin MPs, supporting their potential use in biomedical applications.