Abstract: At present, all known marine-derived 1,6-naphthyridine natural products have been isolated from sponge organisms. Research indicates that these compounds exhibit significant biological activities in various fields, including antitumor, antioxidant, and antibacterial properties, demonstrating broad potential for drug development. This article systematically reviews the sources, chemical structures, biological activities, and mechanisms of action of 42 marine-derived 1,6-naphthyridine natural products. This study aims to systematically summarize the biological activities of these natural products, thereby identifying novel structures and prominent active compounds as potential leads for new drug development. At the same time, these studies lay the foundation for the development of highly effective and low-toxicity new drugs, thereby making an important contribution to human health.