Preference for a cis/trans peptide bond between residues of dipeptides formed by substituted beta(2,3) (I) and beta(3) (II) homoproline is investigated using density functional theory (DFT). Potential energy surfaces for monomer and linear dimers are explored at the B3LYP/6-31G(d,p) level of theory. Minimum energy conformations of the dipeptides are optimized using B3LYP, PBE1PBE, B97D, and M06-2X functionals at the 6-31G(d,p) level of basis set in both the gas phase and solvent phase. The relative free energy difference between the selected conformations is marginal. Results obtained using the functionals M06-2X and B97D on dimers of I and II, respectively, agree with experimental results. The lowest energy conformations predicted by B97D/6-31G(d,p) and M06-2X/6-31G(d,p) levels of theory show greater relative MP2 correlation energy. Dipeptides of I with hydrophilic substituents show preference for a trans peptide bond. Support for cis/trans isomerism in dimers of I with hydrophobic substituents comes from potential energy surfaces and free energy data. Although dipeptides of II with hydrophilic substituents show preference for cis peptide bond, the dipeptides with hydrophobic substituent prefer trans bond.