One of the hypotheses for the homochirality of amino acids in the context of the origin of life is that only a particular stereoisomer provides preferential stability to RNA folding by acting as a chemical chaperon. However, the effect at the molecular level is not well understood. This study provides a molecular understanding of such preferential stability for a small GAAA RNA tetraloop in the presence of chiral arginine through a multidimensional free energy landscape constructed using a combination of umbrella sampling and parallel bias metadynamics (PBMetaD) simulations. We show that the origin of the chirality difference in RNA folding–unfolding dynamics is due to differences in the configurational diversity of RNA in adopting various non-natural conformations that accompany the diverse binding modes of D-arginine and L-arginine. We show that while D-arginine stabilizes the native folded state of RNA, L-arginine destabilizes it. Furthermore, free energy calculations on the binding of D- and L-arginine reveal a specific geometric constraint that helps D-arginine to stack with the terminal base pairs of RNA and pushes L-arginine for groove binding.