Biopolymers, derived from renewable resources, serve as sustainable alternatives to conventional petroleum-based plastics and are widely explored for applications ranging from food packaging to biomedical devices. However, their broader adoption is hindered by certain limitations, including their natural susceptibility to microbial colonization and their relatively poor barrier and mechanical properties compared to synthetic polymers. Fortification refers to the strategic incorporation of antimicrobial agents, nanofillers, or other functional modifications into biopolymers. This approach enhances antimicrobial activity while simultaneously preserving or improving the material’s structural integrity, barrier properties, and overall performance. In this connection, this chapter provides a comprehensive understanding of the rationale behind biopolymer fortification, the underlying mechanisms of action, practical strategies for enhancement, various manufacturing techniques, characterization methods, potential applications, regulatory and safety considerations, and emerging future directions for developing fortified biopolymers with superior antimicrobial functionality.