The global challenge of antimicrobial resistance has prompted innovative approaches in veterinary medicine, particularly the development of drug delivery systems (DDSs) using nanoparticles (NPs). NPs, with their unique properties such as size, morphology, and surface features, have shown promise in addressing bacterial infections, including those caused by multidrug-resistant (MDR) strains and pathogens associated with diseases like mastitis. The potential of NPs as DDSs in veterinary medicine has been widely investigated, offering benefits such as prolonged systemic circulation, increased bioavailability, reduced toxicity, and enhanced therapeutic efficacy. This marks a significant advancement in the treatment of microbial infections in animals. The focus extends to the challenges associated with production, purification, and regulatory approvals, prompting the exploration of biotechnological and nanotechnological approaches using NPs as carriers for bacteriocin delivery. Bacteriocins, or antimicrobial peptides (AMPs), present an alternative to traditional antibiotics and have demonstrated effectiveness against various pathogens. Metal NPs, including silver, zinc oxide, and iron oxide, exhibit notable antibacterial, antiviral, and antifungal activities, providing novel solutions for diseases like mastitis, abortion, and diarrhea in cattle. Their mechanism of action involves disrupting and penetrating the cell membrane of microorganisms, leading to cell death. Additionally, antimicrobial NPs are explored in conjunction with certain antibiotics like florfenicol, doxycycline, and cloxacillin, addressing challenges related to solubility and improving therapeutic efficacy. Solid lipid NPs (SLNPs), nanostructures, and chitosan NPs are investigated for controlled release, enabling targeted drug delivery and heightened antimicrobial activity. Chitosan, a natural polymer, emerges as a favorable nanocarrier due to its biocompatibility and biodegradability. This chapter provides a comprehensive overview of the advances, challenges, and future prospects of NPs in veterinary DDSs, showcasing their potential in transforming the landscape of veterinary medicine.