Xenogenic collagen-based matrices represent an alternative to subepithelial palatal connective tissue autografts in periodontal and peri-implant soft tissue reconstructions. In the present study, we aimed to investigate the migratory, adhesive, proliferative, and wound-healing potential of primary human oral fibroblasts (hOF) and periodontal ligament cells (hPDL) in response to four commercially available collagen matrices. Non-crosslinked collagen matrix (NCM), crosslinked collagen matrix (CCM), dried acellular dermal matrix (DADM), and hydrated acellular dermal matrix (HADM) were all able to significantly enhance the ability of hPDL and hOF cells to directionally migrate toward the matrices as well as to efficiently repopulate an artificially generated wound gap covered by the matrices. Compared to NCM and DADM, CCM and HADM triggered stronger migratory response. Cells grown on CCM and HADM demonstrated significantly higher proliferative rates compared to cells grown on cell culture plastic, NCM, or DADM. The pro-proliferative effect of the matrices was supported by expression analysis of proliferative markers regulating cell cycle progression. Upregulated expression of genes encoding the adhesive molecules fibronectin, vinculin, CD44 antigen, and the intracellular adhesive molecule-1 was detected in hPDL and hOF cells cultured on each of the four matrices. This may be considered as a prerequisite for good adhesive properties of the four scaffolds ensuring proper cell-matrix and cell-cell interactions. Upregulated expression of genes encoding TGF-β1 and EGF growth factors as well as MMPs in cells grown on each of the four matrices provided support for their pro-proliferative and pro-migratory abilities. The expression of genes encoding the angiogenic factors FGF-2 and VEGF-A was dramatically increased in cells grown on DADM and HADM only, suggesting a good basis for accelerated vascularization of the latter. Altogether, our results support favorable influence of the investigated collagen matrices on the recruitment, attachment, and growth of cell types implicated in oral soft tissue regeneration. Among the four matrices, HADM has consistently exhibited stronger positive effects on the oral cellular behavior. Our data provide solid basis for future investigations on the clinical application of the collagen-based matrices in surgical periodontal therapy.