Non-covalent interactions (NCIs) like π-π stacking interactions, H-bonding, halogen bonding, anion-π interactions, XH-π interactions are ubiquitously found in both chemical and biological domains and extensively used to build new molecules and materials. 1 NCIs involving aromatic functional groups lead to molecular recognition, catalysis, stereo- and regioselectivity of the products. In a recent study we predicted the unique role of indole molecules which stabilizes the transition states during the dehydrogenation process of polyfluorinated alcohols, through non-covalent π-π and Hbonding interactions. 2 This study put forth a straightforward protocol to develop biologically relevant fluoroalkyl bis-indoles in a sustainable fashion through in-depth insights gained from extensive DFT predictions. Furthermore, our latest study unfurls the crucial role of NCIs in electrochemical synthesis of unsymmetrically substituted NH-pyrroles from enamines.3 Trifluoroethanol additives are found to have “magical effect” on tuning oxidation potential of enamines through H-bonding and C-H···π interactions, thus facilitating the desired chemo-selective cross-coupling. Lastly, we discuss how NCIs underpin chirality in bifunctional squaramide catalyzed reactions leading to skeletal diversity in synthesis of azocine derivatives.