Adeno-associated virus (AAV)-based gene therapies hold broad application prospects in the treatment of rare and genetic diseases. However, emerging safety concerns such as dose-dependent immune responses, target organ toxicity, and genomic integration have increasingly become apparent, significantly limiting their clinical translation. This article begins by examining the major manifestations of AAV vector toxicity, delvesinto the mechanisms by which factors such as capsid structure, genome design, and expression regulation contribute to toxic responses, and provides a systematic review of the advances in current mainstream detection technologies—including droplet digital PCR, single-cell RNA sequencing, bioluminescence imaging, and liquid biopsy—for toxicity identification and monitoring. Furthermore, it explores mitigation strategies such as capsid engineering, route of administration optimization, immune modulation, and personalized interventions. The paper proposes a conceptual "design-monitor-intervene" closed-loop control framework, aiming to offer valuable insights for safety evaluation, clinical application optimization, and regulatory strategy development of AAV-based gene therapeutics.