Osteosarcoma (OS) is the most prevalent primary cancer of bone tissues. Gallic acid (GA), a natural phenolic acid found in foods and herbs, has known antioxidant and anti-inflammatory properties, but its role in OS remains unclear. This study evaluated GA's anticancer activity in MG63 osteosarcoma cells, investigating effects on migration, apoptosis, proliferation, and cell cycle progression. Flow cytometry and RT-PCR identified involvement of the JAK-STAT signaling pathway. Molecular docking demonstrated GA's binding affinity toward JAK-STAT proteins. GA inhibited invasion and metastasis, induced cell cycle arrest, and triggered apoptosis, thereby suppressing OS cell growth. Findings indicate that GA regulates JAK-STAT, TGF, and SMAD pathways to impede tumor progression in vitro. © 2025 Elsevier B.V., All rights reserved.