Prevention of fibrosis during the oral mucosal wound regeneration is a pressing issue of today’s surgical dentistry. The study was aimed to perform morphological assessment of the effects of biocompatible piezoelectric membranes on fibrous tissue formation during regeneration of the oral mucosal wounds. We assessed cell–cell interactions of macrophages and fibroblasts, along with changes in the CD68 and TGFβ1 marker expression and their effects on the development of fibrosis under conditions of using biocompatible polymeric membranes with piezoelectric properties at various stages of the oral mucosal wound defect regeneration. Comparative morphological assessment of the oral mucosal structures was conducted in animals having intact mucosa (n = 15), having open wound defects (n = 15), and having wounds covered with biocompatible piezoelectric membranes (n = 15). Biomaterial was collected from the wound defect site on days 3, 7, and 12 of the experiment; collection of biomaterial from intact animals was performed on the same days. In the group, where biocompatible membranes were used, signs of proliferation phase at the defect site were detected as early as on day 3 of the study; the faster shift from macrophage infiltration to fibroblast infiltration, the decline in inflammatory response were detected on day 7; restoration of the numerical density of macrophages and fibroblasts to the intact values was detected on day 12. The expression of CD68 and TGFβ1, the prognostic markers of fibrosis, was lower in the group, where no membranes were used. Reduction of the dense fibrous connective tissue specific area was observed at the microscopic level, severe soft tissue deformation was reported at the macroscopic level. In the group with no wound covering, extensive cell infiltration and increased CD68 and TGFβ1 expression persisted throughout the experiment, which resulted in the fact that specific area of dense fibrous connective tissue was larger, than that of loose connective tissue, on day 12 of the study, as well as in the cicatricial soft tissue deformities.