The role of nanomedicine in disease diagnosis and treatment is indispensable. The future of nanomedicine in the pharmaceutical field is promising owing to its specificity and potency. However, its function and ultimate efficiency in clinical applications are still unsatisfactory, which can be attributed to the toxicity of nanomaterials caused by their nondegradability and accumulation in the body. To overcome the obstacles associated with the synthesized materials, researchers have focused on natural phytochemicals with good biodegradability, biocompatibility, and self-assembly capability. The structural diversity and combinational therapeutic effects of natural phytochemicals have broadened their nanomedical applications. This Review summarizes natural phytochemical-based nanostructures, including steroids, terpenoids, alkaloids, flavonoids, quinones, and polysaccharides and highlights their enormous application potential in nanomedicines. Additionally, in this Review, we summarize recent advances in nanostructures based on natural phytochemicals and introduce representative examples for drug-delivery, imaging, and theranostic applications in nanomedicine. Finally, we discuss the challenges in the rational design, synthesis, and fabrication of natural phytochemical-based nanostructures and propose feasible solutions for problems that need to be overcome to enable clinical translation.