Breast cancer is the most common kind of cancer among women worldwide and is a malignancy that develops from the breast epithelial tissue. The Estrogen Receptor Alpha (ER-α) has been linked to the diverse signaling pathway that controls the proliferation, differentiation, and survival of breast cancer cells. Accordingly, it is crucial to focus on the ER-α as an important target for diagnosis, as well as to establish treatment strategies for these ailments. This study carried out an in-silico investigation of the potential inhibitory activity of ten secondary metabolites in soursop leaves (Annona muricata Linn) against ER-α. The experiments were conducted using a variety of computational approaches, namely ligand-based pharmacophore screening, molecular docking, as well as the prediction of their physicochemical and pharmacokinetic properties using Lipinski's Rule of Five and ADME-Tox software. The result demonstrated that daidzein exhibited a free binding energy of -8.56 kcal/mol and an inhibition constant of 513.26 nM. The visualization of docking results showed that daidzein was found to interact via hydrogen bond interactions with several amino acids in the ER-α binding site, such as GLY521, HIS524, and GLU353. Thus, it can be concluded that among the ten compounds studied, daidzein may have the potential to be further studied as a candidate for ER-α inhibitor.