The latest advances with natural products in drug discovery and opportunities for the future: a 2025 update

INTRODUCTION: The landscape of drug discovery is rapidly evolving, with natural products (NPs) playing a pivotal role in the development of novel therapeutics. Despite their historical significance, challenges persist in fully harnessing their potential in the development of modern medicine. AREAS COVERED: This perspective discusses the recent advances and opportunities in NP-based drug discovery. This includes exploration of the recently approved representative NP-derived drugs, innovative target identification strategies and advancements in hybrid NP molecules for addressing complex diseases. Moreover, the authors also discuss the role of NP-derived payloads in antibody-drug conjugates (ADCs) for targeted cancer therapy. This article is based on searches using the FDA and DrugBank database as well the Derwent Innovations Index from Web of Science between the period of 2017 to 2025. EXPERT OPINION: NPs remain vital to drug discovery, demonstrating adaptability in tackling complex medical challenges. Future efforts should focus on integrating advanced methodologies, such as artificial intelligence (AI), high-throughput screening, chemical biology, bioinformatics, gene regulation, the highly accurate non-labeling chemical proteomics approach to explore novel NPs targets. Emphasizing these developments will be crucial for maximizing the therapeutic potential of NPs in combating unmet medical needs.