RHO and neoplasm: We demonstrate that Mg–PCL–MT could benefit the tumor suppression of melatonin, and our novel melatonin-loaded Mg–PCL scaffolds synergistically inhibited the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus exerted an anti-invasion and anti-metastasis effect on OS cells.