A safe and low-toxic γ-CD-MOFs was firstly synthesized by an improved hydrothermal method in this study, and then the drug-loaded γ-CD-MOFs (Cur@CD-MOFs) were prepared through in situ adsorption, using curcumin (Cur) as drug model. Finally, polyethylene glycol-functionalized chitosan (CS-g-mPEG) was used to modify Cur@CD-MOFs to form cyclodextrin supramolecular composites (Cur@CD-MOFs/CS-g-mPEG). The structure and morphology were characterized by FT-IR, XRD, TGA, N2 adsorption, and SEM. In addition, the stability, in vitro drug release, antioxidant, antibacterial, and biocompatibility properties were investigated. The results showed that curcumin was loaded into γ-CD-MOFs with drug loading capacity of 43.86 ± 1.63% and encapsulation efficiency of 29.48 ± 3.56%, and the release rate after 120 h was 33.2%, under the conditions of pH = 1.2 and 37 °C. Besides, CS-g-mPEG modified Cur@CD-MOFs were successfully prepared, which had excellent mesoporous properties, thermal stability, and bioavailability. After modification, the DPPH free radical scavenging rate after 30 min was 59.4%, compared with pure Cur of 49.1%; the inhibition rate against Escherichia coli and Staphylococcus aureus was 98%, and the cell proliferation rate after 48 h was 98.7%, showing enhanced antioxidant, antibacterial, and biocompatibility properties. These cyclodextrin supramolecular composite materials can be widely applied as low-toxicity, edible and effective drug delivery system in the food and pharmaceutical industries.