Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed.