Objective <p>This study aimed to evaluate and compare the concentrations of Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), and Transforming Growth Factor (TGF) in platelet-rich fibrin (PRF) biomaterials obtained from individuals with various systemic diseases.</p> Materials and Methods <p>A total of 65 individuals were included and divided into five groups: healthy controls (n = 13), patients diagnosed with diabetes (n = 13), patients receiving bisphosphonate therapy (n = 13), patients using immunomodulatory drugs (n = 13), and patients diagnosed with hepatitis (n = 13). PRF samples were collected from each participant and analyzed in a biochemistry laboratory using ELISA kits specific to PDGF, VEGF, and TGF. The growth factor concentrations were statistically compared across the groups.</p> Results <p>The highest mean concentration of PDGF was observed in the hepatitis group. The highest mean concentrations of VEGF and TGF were found in patients using immunomodulatory drugs. However, the differences in growth factor concentrations among the groups were not statistically significant.</p> Conclusion <p>PRF is an effective biomaterial widely used in dentistry due to its rich content of growth factors. While no statistically significant differences were found in growth factor concentrations among individuals with different systemic conditions, a notable increase in these levels was observed in certain disease groups. These findings suggest that systemic diseases may influence the biological composition of PRF, warranting further investigation.</p>