Singapore, despite its small size and highly urbanized environment, hosts a remarkable diversity of marine life, including coral reefs, mangroves and seagrass meadows. However, extensive coastal development, pollution and climate change have significantly impacted these ecosystems, leading to habitat loss and biodiversity shifts. This chapter provides an overview of Singapore’s marine biodiversity, current status on marine drug discovery as well as highlights several research initiatives related to marine microbiome as sources of new drug agents. Local marine organisms, such as corals, sponges, tunicates and cyanobacteria, are rich sources of bioactive compounds with pharmaceutical potential, including antimicrobial, anticancer and antiinfective agents. Advances in biotechnology and molecular techniques have enabled researchers to explore the chemical diversity of marine organisms, uncovering novel compounds with applications in medicine, biotechnology and environmental management. The chapter also discusses the challenges facing marine natural products research in Singapore, such as limited marine biodiversity, high research costs and sustainability concerns. To address these challenges, the integration of innovative technologies, including metabolomics, genomics, synthetic biology, and artificial intelligence, is proposed. By balancing ecological protection with scientific innovation, Singapore aims to ensure the long-term viability of its marine resources while contributing to global advancements in marine natural products research.