Apigenin (APG), a natural flavonoid compound with anti-inflammatory and antioxidative properties, was found to promote in vitro osteogenic differentiation and to accelerate in vivo bone formation, indicating APG as a promising molecule in bone repair, with potential clinical application in bone-deficient conditions. In particular, in dentistry, it is fundamental to increase the available bone volume for implant placement in the maxilla. Therefore, this study aims to investigate the APG effects on osteoblasts (hOBs) obtained from a human jaw. hOBs were incubated with increasing concentrations of APG (5, 10, 20 µM) to assess cell viability and morphology at 24 h and proliferation at 48 and 72 h. Upon establishing the absence of cytotoxicity and any morphological changes, APG showed a stimulating effect on cell growth, with significative results using 5 µM (5-APG) at 48 h. Thus, 5-APG was chosen for further investigations in order to assess alkaline phosphate (ALP) at 7 days, mineralization at 14 days and expression of ALP, Osteocalcin (OCN) and Collagen 1 (COL1) genes at 7 days. Our results showed that 5-APG accelerated osteoblast mineralization activities and significantly upregulated ALP and COL1 gene expression. Hence, this study demonstrated that APG is able to promote human oral osteoblasts proliferation and mineralization, suggesting its potential usefulness in dentistry.