A one-step synthesis of a curcumin-derived hydrogel (curcumin content of 25-75 mol %) is reported. Curcumin is incorporated into the hydrogel backbone and cross linked through biodegradable carbonate linkages. Curcumin as a part of the polymer backbone is protected from oxidation and degradation, while hydrogel hydrolysis results in the release of active curcumin. Nontoxic poly(ethylene glycol) and desaminotyrosyl-tyrosine ethyl ester are used to tune the hydrophilic/hydrophobic hydrogel properties. In this way, hydrogels with a wide range of physical properties including water uptake (100-550%) and compression moduli (7-100 kPa) were obtained. Curcumin release is swelling controlled and could be extended to, 80 days. In vitro, curcumin-derived hydrogels showed selective cytotoxicity against MDA-MB-231 (IC50 9 mu M) breast cancer cells but no cytotoxicity to noncancerous quiescent human dermal fibroblasts even at high curcumin concentrations (160 mu M). One possible application of these curcumin-derived hydrogels is as soft tissue filler after surgical removal of cancerous tissue.