Cyclodextrins are a class of widely used starch-derived host molecules applied in many areas of everyday life, such as pharmacy, cosmetics, and food industry. β-Cyclodextrin is suitable for encapsulating the gadolinium cation, levofloxacin or the complex between the metal and the fluoroquinolone antibiotic, thus forming 1:1 and/or 1:1:1 inclusion structures. Understanding the underlying processes of recognition is of great importance, since Gd³⁺ finds broad application as an NMR contrasting agent and the simultaneous intake of gadolinium and levofloxacin may affect the action of the drug. The current molecular modeling study sheds light on essential aspects on the host-guest recognition by employing a combined DFT/SMD methodology. Significant factors such as presence/absence of a hydration shell around the metal cation, ionization of the levofloxacin molecule and dielectric constant of the surrounding medium are taken into account. The obtained results outline additional future perspectives in the gadolinium complexation abilities and its use as a calcium mimetic species in biological systems.