The results of in vivo immersion optical clearing of human skin under the action of two different optical clearing agents (OCAs), such as an aqueous sucrose solution and a radiographic contrast agent Omnipaque™ 300 (iohexol), were obtained with the use of optical coherence tomography (OCT) method. The rate of reduction of light scattering coefficient, obtained through an averaged A‐scan of the OCT image in the region of dermis within the depths from 350 to 700 μm, were determined to evaluate the efficiency of optical clearing (EOC). The correlations between the EOC and the energy of intermolecular interaction of OCAs with a fragment of collagen peptide have been established as a result of molecular modeling by quantum chemistry methods HF/STO3G/DFT/B3LYP/6—311G(d) of a number of OCAs (glycerol, iohexol, sucrose, ribose, fructose, glucose) with mimetic peptide of collagen (GPH)3.