The application of natural small products with self-assembly characteristics in a drug-delivery system is attractive for biomedical applications because of its inherent biological safety and pharmacological activity, and there is no complex structural modification process. However, drug carriers with pharmacological effects have not been developed enough. Here, we report a pure natural nanomedicine-cum-carrier (NMC) drug delivery system. The NMC is formed by the direct co-assembly of two small molecular natural compounds through noncovalent interaction, and a molecular dynamics model for predicting the co-assembly of two small molecular compounds was established. The representative co-assembled NMC (oleanolic acid and glycyrrhetinic acid) not only shows excellent stability, high drug loading, and sustained release characteristics but also the co-assembled NMC formed by two small molecular compounds has a synergistic antitumor effect (CI < 0.7). After drug loading, the antitumor effect is further improved. In addition, this NMC highlights the unique advantages of active natural products in biosafety and health benefits. Compared with free drugs, it can reduce the liver damage caused by chemotherapy drugs through upregulating key antioxidant pathways. Compared to nonpharmacologically active drug delivery systems, it can reduce the risk of nanotoxicity. Taken together, this co-assembly drug-carrier system overcomes the shortcomings that pharmacologically active compounds cannot be directly applied, enhances the pharmacological activity of bioactive drug carriers, improves the antitumor efficacy, and slows down the side effects induced by chemotherapy drugs and the additional toxicity caused by long-term use of non-bioactive nanocarriers.