Fabrication of biocompatible scaffolds that can facilitate the mending of damaged tissue has attractedmuch attention. In this study, the preparation and structural investigation of a curcumin-loaded Fe(II)metal–organic framework/polydimethylsiloxane sponge, Cur/Fe-MOF/PDMS, are reported. Various techniquessuch as FTIR (Fourier-transform infrared), XRD (X-ray diffraction), SEM (scanning electron microscope),TEM (transmission electron microscope), EDS (energy-dispersive X-ray spectroscopy) mapping,and XPS (X-ray photoelectron spectroscopy) have been used to investigate the as-fabricated materials. Results confirm the successful incorporation of curcumin and Fe-MOF into the PDMS matrix. Theobtained SEM images indicate the sponge-like structures of the PDMS and the Fe-MOF/PDMS composite. Indeed, the results from in vivo show animals all to be survived without any unusual responses to thetransplant. According to macroscopic observation, the Fe-MOF/PDMS and Cur/Fe-MOF/PDMS scaffoldsseem better confederates than the pure PDMS. H&E staining has confirmed enhanced healing and revascularizationin the Cur/Fe-MOF/PDMS than the PDMS and Fe-MOF/PDMS scaffolds. Additionally, a twostageprofile was observed for the release of curcumin into PBS (phosphate-buffered saline) solution. The hydrophilic property of the Fe-MOF resulted in fast release at the first stage. These results exhibit thatthe Cur/Fe-MOF/PDMS sponge can serve as a 3D porous substrate in the tissue engineering (TE) field.