Bisphosphonates are frequently used for the antiresorptive treatment in bone metastasis diseases or for osteoporosis. A side effect of this therapy is osteonecrosis of the jaw. This inhibits osteoclast function, but osteoblasts and fibroblasts are also negatively affected in terms of impaired proliferation. Additive local treatment with platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) promotes adhesion, proliferation and migration of cells due to high concentrations of growth factors like PDGF, TGF and IGF. The aim of the study was to investigate the effect of PRP or PRF on proliferation, migration and viability of osteoblasts and oral fibroblasts, treated with zoledronic acid (ZA). ZA treated fibroblasts and osteoblasts were exposed to PRP/PRF. Cell proliferation, migration and viability were measured using the real-time cell-analyzer assay (RTCA), the scratch assay and the MTT assay. There was a significant increase in closure of the scratch area by PRP/PRF treated osteoblasts (PRP = 40.6%, PRF = 100.0%, NC = 0.0%) as well as fibroblasts (PRP = 100.0%, PRF = 100.0%, NC = 12.7%) in comparison to the group of negative control (all p ≤ 0.05). Furthermore, the negative effect of ZA on cell migration was generally reduced in both cell lines using PRP/PRF. The viability and proliferation of cells decreased after exposure to ZA, whereas we observed an enhancement of cell viability within 24 hours by application of PRP/PRF in ZA treated cells. The negative effect of ZA on cell proliferation was especially reduced when using PRF. The use of PRF/PRP improves the behavior of ZA-treated cells, but PRF appears to have an advantage in comparison to PRP. This study demonstrates that treatment with PRF/PRP may have positive effects in the therapy of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ).