Organoids are multicellular organ models that are self-organized and derived from stem cells or primary tissues in specific three-dimensional (3D) environments. Cancer patient-derived organoids (CPDOs) retain key characteristics of the original tumor, including genomic, epigenetic, and metabolic profiles, while accurately recapitulating the human tumor microenvironment (TME) - closely mirroring features observed in patient tumors. Compared to traditional cell lines and animal models, CPDOs offer significant advantages, making them increasingly valuable for cancer research and precision medicine. Meanwhile, natural products (NPs) remain a rich and pharmacologically promising source of anticancer drug candidates. In this review, we systematically summarized the important applications of different CPDOs in the efficacy evaluation, drug screening, and mechanism studies of NPs. Moreover, we also discussed the advantages, limitations, and future perspectives of CPDOs, proving valuable insights for researchers and clinicians in this field.