Vibrio infection is a longstanding and serious bacterial disease of various shellfish species that has caused high mortality rates for many decades. Antibiotics can effectively prevent and control bacterial diseases. However, the long-term abuse of antibiotics exacerbates the risk of environmental pollution, which also poses a threat to food safety. In this study, transgenic lines of the marine microalga Tetraselmis subcordiformis harboring antimicrobial peptide NZ2114 were attempted to be created as an oral drug-delivery system in shellfish aquaculture. Toward this, codon-optimized nz2114 was respectively assembled into nuclear and chloroplast expression vectors of T. subcordiformis. After particle bombardment, two stable transgenic lines Y1 (with nuclear transformation) and Y2 (with chloroplast transformation) were selected, each expressing a stable transgene inheritance for at least 12 months. In vitro experiments demonstrated the significant inhibition of total protein containing NZ2114 from transgenic lines on two marine Vibrio species and Staphylococcus aureus. To test the efficacy of transgenic baits, pathogen-infected scallops (Argopecten irradians) were fed with transgenic T. subcordiformis via oral delivery. The results showed that the survival rate (after 20 days of infection) of the scallops fed transgenic T. subcordiformis was much higher than that of scallop fed with wild-type algae (95.92% versus 80.41%). In summary, this strategy offers a new, efficient, and low-cost method for controlling Vibrio in scallop aquaculture through oral drug-delivery system, which is a promising step toward the development of safe and environment-friendly antimicrobial baits.