The aim of the systematic review was to analyze the use of combination of bone substitutes and vectors in periodontology and implantology among animals models and humans. Electronic databases were searched, and additional hand search was performed. The research strategy was achieved according to the PRISMA guidelines. The including criteria were: combination of bone substitutes and vectors, in vivo studies, a precise number of specimens, histological and radiographic analysis, written in English. The risk of bias was evaluated for individual studies. Thirty-two articles were selected and investigated in this systematic review. The results do not show a superiority of the use of composite biomaterial in comparison with simple biomaterial but suggest the efficacity of their utilization as a carrier of bioactive agents. Future studies need to identify the suitable association of bone substitutes and vectors and explore interest in their use such as the support of growth factors.