The image contrast and probing depth of optical methods applied to in vivo skin could be improved by reducing skin scattering using the optical clearing method. The aim of this study was to quantify, from line‐field confocal optical coherence tomography (LC‐OCT) 3D images, the modifications of skin scattering properties in vivo during optical clearing. Nine mixtures of optical clearing agents were used in combination with physical and chemical permeation enhancers on the human skin of three healthy volunteers. Scattering coefficient and anisotropy factor of the epidermis and the upper dermis were estimated from the 3D LC‐OCT images of skin using an exponential decay model of the in‐depth intensity profile. We were able to demonstrate a decrease in epidermal scattering (down to 33%) related to optical clearing, with the best results obtained by a mixture of polyethylene glycol, oleic acid, and propylene glycol.