Occlusal trauma can be generated by a number of local factors, including incorrect dental prosthetic systems. Proper therapy can lead to improved tissue homeostasis, with an increase in bone neoformation, whose markers include the N-terminal procollagen I propeptide (PINP). The purpose of the study was to determine serum N-terminal procollagen I propeptide levels in patients with occlusal trauma caused by incorrect prosthetic systems, performed before and after the establishment of perio-prosthetic complex therapy. The study was performed on a group of 56 patients with periodontal disease and prosthetic systems generating nonphysiological, traumatic occlusal forces. These patients underwent the clinical examination, appropriate multidisciplinary therapy, and N-terminal procollagen I propeptide levels were evaluated in the serum at baseline, 6 months, and 12 months after the therapy completion. The results demonstrated significant improvements for periodontal parameters in both post-treatment assessments and an increase in N-terminal procollagen I propeptide, more significant at one year after treatment.