The solvation of two different antibiotics (ampicillin and piperacillin) in three newly designed arginine-based deep eutectic solvents (DESs) is studied using computational chemistry methods: molecular dynamics simulations and quantum chemistry calculations. The main features of intermolecular forces and structural characteristics between the antibiotics and the solvents are characterized in order to justify the large affinity of ampicillin and piperacillin molecules for selected DESs, with the emphasis on the hydrogen bonding, with respect to strength, deviations of ideality, topological properties, interaction patterns and how they occur, structuring of the solvation shells and their analysis regarding dynamic properties. Arginine (Ar) is combined with glutamic acid (Ga), oxalic acid (Oa), and tartaric acid (Ta) to form DESs (ArGa, ArOa, ArTa), and they are coupled with ampicillin (Ap) and piperacillin (Pp). Results shared in this work allow to deduce on the effective solvation of antibiotics in DESs because of strong solute-solvent intermolecular interactions accompanied by a slight volume expansion and minor solvent structural changes, thus, confirming these solvents as suitable materials for antibiotic drug delivery in the liquid phase