Breast cancer is still considered one of the most common malignancies worldwide, requiring the continual development of novel targeted therapeutic agents. This study reports the insilico design, molecular docking, and the ADME analysis of four novel coumarin-pyrazoline-sulfonamide hybrid derivatives (D–G) as potential anti-breast cancer drugs targeting the estrogen receptor alpha (ERα). The four compounds contain different aryl substituents phenyl (D), 4-hydroxyphenyl (E), 4-methoxyphenyl (F), and 4-fluorophenyl (G) at the C-5 position of the pyrazoline ring attached to the coumarin substrate, but the N-1 position carries a 4-aminosulfonylphenyl group. Molecular docking simulations were performed against the ERα ligand-binding domain (PDB: 1ERR) using the Glide Standard Precision procedure within the Schrödinger software suite, with olaparib as the drug of reference. Each of the four designed compounds showed higher binding affinities compared to olaparib (−7.130 kcal/mol). The most favorable Glide score of −7.727 kcal/mol was obtained from the compound E (4-hydroxyphenyl derivative), which was following compounds D (−7.448 kcal/mol), F (−7.257 kcal/mol), and G (−7.192 kcal/mol). Key interactions included hydrogen bonding with Glu353, Asp351, Arg394, Thr347, and His524, in addition to extensive hydrophobic contacts within the ERα bonding pocket. These findings were further corroborated by MM- GBSA calculations, wherein the compound exhibited the highest complex stability with a binding free energy of -65.4 kcal/mol, compared to other derivatives (D, F, and G) and the reference compound (-67.37 kJ/mol). ADME profiling utilizing SwissADME confirmed all compounds comply with Lipinski’s Rule of Five with no violations and exhibit favorable pharmacokinetic characteristics. These results demonstrate the promising importance of engineered coumarin derivatives, particularly compound (E), as lead structures for future development as proliferative inhibitors targeting estrogen receptor alpha (ERα).