β-Blockers are used globally for the treatment of cardiovascular problems. Unfortunately, these are consumed as racemic mixture causing serious side effects due to the presence of unwanted enantiomers. A simulation study of some commonly used β-blockers was carried out at supramolecular level to understand stereo-selective binding of β-blockers with receptors (β-ARs). The values of docking energy ranged from 6.58 to 9.11 and 7.05 to 9.15 kcal/mol for R- and S-enantiomers, respectively. Mostly, S-enantiomers bind stronger with β-ARs (in terms of docking energy) than their Rantipodes, with some exceptions. The results of docking study indicated higher pharmaceutical potencies of S-enantiomers than R-antipodes.