Phenylketonuria (PKU) is an inherited metabolic disorder characterized by deficient activity of phenylalanine hydroxylase, leading to toxic accumulation of phenylalanine. Current therapies rely primarily on dietary restriction or enzyme substitution, but long-term compliance and systemic side effects remain challenges. Recent advances in synthetic biology and probiotic engineering have enabled the development of live biotherapeutic products (LBPs) capable of in situ metabolic correction. Lactococcus lactis, a Gram-positive, non-colonizing, and generally recognized as safe (GRAS) bacterium, has emerged as a promising chassis for plasmid-based delivery of therapeutic enzymes. This review explores the biological features of L. lactis, plasmid engineering strategies, mechanisms of gastrointestinal delivery, preclinical and clinical evidence supporting microbial therapeutics, biosafety and regulatory considerations, and future perspectives for PKU treatment. Emphasis is placed on plasmid-mediated expression of phenylalanine ammonia-lyase (PAL) and strategies to enhance luminal phenylalanine degradation while maintaining host safety. The review integrates recent findings and key studies over the past five years to highlight the translational potential of L. lactis in metabolic biotherapy.