Abstract: In recent years, the field of nucleic acid therapeutics has been flourishing, progressively establishing itself as the third generation of drug modalities following small molecules and antibody-based drugs. Artificial intelligence technology based on machine learning is advancing rapidly, which can significantly accelerate the development process of nucleic acid therapeutics. This review provides an overview of the foundational aspects of artificial intelligence algorithms, databases, and characterizations in the field of nucleic acid drug development. It elucidates the advances in the application of artificial intelligence in nucleic acid structural prediction, small nucleic acid drug design, and other research and development phases of nucleic acid therapeutics, aiming to offer some reference for the interdisciplinary development of artificial intelligence and nucleic acid drugs.