The development of nanoparticles that are stable and permit high levels of controlled drug release into specific cancer cells still remains challenging. Herein, we reported that supramolecular nanoparticles assembled through host-guest interaction comprised of β-cyclodextrin (β-CD), polypropylene glycol (PPG), and folic acid (FA) to form FA-PPG-β-CD supramolecular nanoparticle encapsulated with an anticancer drug magnolol. The resulting nanoparticle exhibited spontaneously self-assembly into nanosized and relatively stable nanostructure in an aqueous solution. Interestingly, magnolol released from FA-PPG-β-CD supramolecular nanoparticles could be precisely adjusted via tuning the temperature, making exceedingly desirable candidates for controlled drug delivery applications. Moreover, the cytotoxicity study clearly demonstrated that FA-PPG-β-CD supramolecular nanoparticles had very low toxicity under normal cells but were very harmful towards cancer cells. More importantly, cellular uptake experiments confirmed that magnolol-loaded FA-PPG-β-CD nanoparticles significantly improved selective intracellular uptake and enhanced the chemotherapeutic efficacy in cancer cells. Therefore, FA-PPG-β-CD supramolecular nanoparticles provide well-controlled drug release, subsequently enhancing the efficacy of chemotherapeutic cancer.