Objectives: CDK2 is a protein that plays a role in regulating the cell cycle where its overexpression contributes to uncontrolled cell proliferation. Inhibition of CDK2 has been known to be one of the mechanisms of various anticancer drugs. Curcumin is an active compound of Curcuma Longa which have been reported to inhibit the activity of Cyclin D, Cyclin E, CDK2, CDK4, and CDK6. Material and Methods:This study aims to design more active curcumin derivatives as anticancer drugs by targeting CDK2 through a molecular modelling approach. In brief, the process consist of receptor and ligand preparation, method validation, pharmacophore modelling, and docking simulation. Results:The results of molecular docking simulation show that the free bonding energy (∆G) of curcumin and kurkumod 23 and 24 (the best modification of curcumin) are -7.80, -9.15, and -9.36 kcal/mol respectively. The hydrogen interaction between kurkumod 23 and 24 with CDK occurred on Lys33 residue which is considered as a potential interaction side for CDK2 inhibitor compounds. Pharmacophore modelling showed that kurkumod 23 and 24 have a pharmacophore-fit value of 45.20% and 47.26% respectively. Conclusion:Based on the study result, it can be considered that kurkumod 23 and 24 are the best and most potential modifications of curcumin as CDK-2 antagonist, which is based on the interactions that occur between these two derivatives with amino acid residues from the CDK2 receptor.