Background: Osteoporosis is an imperative health problem that extremely distresses the public that leads to a higher risk to the bones from both spontaneous and accidental bone fractures. Caffeic acid is a polyphenol compound that happens naturally in numerous vegetables such as coffee beans, potatoes, propolis, olives, and carrots with many pharmacological aids. Objectives: The current study was planned to examine the potential of Caffeic acid in proliferation, differentiation, and calcium mineralization of osteoblast-like MG-63 cells. Materials and Methods: The cell viability of Caffeic acid-supplemented MG-63 cells was examined through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity test. The mRNA expression of alkaline phosphatase (ALP) and osteocalcin was reviewed through reverse transcription polymerase chain reaction study. The calcium deposition rate in the Caffeic acid-treated MG-63 cells was studied through Alizarin Red S (ARS) staining. Results: The result of the MTT test exposed that the 10 and 20 mg/kg of Caffeic acid supplementation did not show any cytotoxicity to the osteoblast-like MG-63 cells; instead, it helped the viability of MG-63 cells. The expression of ALP is particularly increased in the Caffeic acid-supplemented MG-63 cells, whereas the osteocalcin expression was noticeably diminished. The ARS staining was exhibited that the Caffeic acid treatment was noticeably enhanced the calcium mineralization rate in the osteoblast-like MG-63 cells. Conclusion: Based on the findings of investigation, it was proved that the Caffeic acid treatment was significantly enhanced the cell proliferation, differentiation, and calcium mineralization in the osteoblast-like MG-63 cells. Hence, it was clear that Caffeic acid can be engaged as the potential agent for the purpose of bone regeneration.