The health of peri-implant soft tissues is important for the long-term success rate of dental implants and the surface topography is pivotal in influencing it. Thus, the aim of this study was to evaluate, in human patients, the inflammatory mucosal microenvironment in the tissue surrounding a new, nanoscale, laser-treated healing abutment characterized by engineered nanopores versus a standard machined-surface. Analyses of anti- and pro-inflammatory markers, cytokeratins, desmosomal proteins and scanning electron microscopy were performed in 30 soft-tissue biopsies retrieved during second-stage surgery. The results demonstrate that the soft tissue surrounding the laser-treated surface was characterized by a lower grade of inflammation than the one facing the machined-surface, which, in turn, showed a disrupted epithelium and altered desmosomes. Moreover, higher adhesion of the epithelial cells on the laser-treated surface was detected compared to the machined one. In conclusion, the laser-treated surface topography seems to play an important role not only in cell adhesion, but also on the inflammatory makers’ expression of the soft tissue microenvironment. Thus, from a clinical point of view, the use of this kind of topography may be of crucial importance not only on healing abutments but also on prosthetic ones.