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Natural products have historically played a crucial role in drug discovery, leading to groundbreaking therapies such as paclitaxel, artemisinin, and reserpine (Atanasov et al., 2015; Nasim et al., 2022). However, their transition from laboratory discovery to clinical application remains a significant challenge, including structural complexity, limited scalability, and regulatory hurdles (Fernandez-Moure, 2016). This review explores innovative interdisciplinary strategies to overcome translational barriers in natural product-based drug discovery, integrating metabolomics, genomics, computational tools, and synthetic biology to accelerate drug development (Salem et al., 2020). We highlight case studies from biodiversity-rich nations, Indonesia and Madagascar, where local innovations are helping to bridge the gap between discovery and application. In Indonesia, platforms such as the RAMES Library and the National Genome Project enable rapid metabolomic and genomic screening of native medicinal plants. In Madagascar, synthetic biology approaches applied to Catharanthus roseus and Rauvolfia serpentina illustrate how endemic biodiversity can be leveraged through virus-induced gene silencing and in vitro biosynthesis techniques. Furthermore, we discuss sustainability challenges, biotechnological advancements for scalable production, and AI-driven methodologies aimed at optimizing clinical trials design (Chopra et al., 2023). Regulatory challenges across different jurisdictions, including the FDA (U.S. Food and Drug Administration) (U.S), EMA (European Medicines Agency) (Europe), and CFDA (China Food and Drug Administration) (China), are discussed to provide a global perspective on natural product commercialization (Tresina et al., 2021). The review underscores the need for international collaboration, open-access data sharing, and innovative clinical trial methodologies to enhance efficiency and reduce drug development timelines. By integrating cutting-edge science with sustainability and ethics, the full therapeutic potential of natural products can be unlocked, transforming them into impactful, accessible medicines.

Natural products; Drug Discovery, Clinical Translation, Indonesia, Madagascar, Therapeutics