Osteosarcoma (OS) is the most common primary malignant bone tumor mainly occurring in children and adolescents. In past decades, studies revealed that PARK2 was a vital tumor suppressor gene in many malignant solid tumors. However, the role of PARK2 in OS remains largely unclear. Therefore, we assessed PARK2 expression in OS tissue and adjacent non-tumor tissues by immunohistochemical (IHC) analysis, and evaluated PARK2 mRNA expression in OS cell lines by real-time PCR analysis. The HOS and U2OS cell lines were employed to establish a PARK2 overexpression model. Using this model, we investigated the potential role of PARK2 in OS and explored the underlying molecular mechanisms. Our study showed PARK2 was downregulated in OS tissue and cell lines, which was significantly associated with higher tumor stage (P < 0.05). Overexpression of PARK2 arrested the cell cycle, inhibited cell proliferation, migration, and invasion, induced cell apoptosis, and reduced tube formation in vitro. Moreover, overexpression of PARK2 significantly suppressed tumor growth and angiogenesis in vivo. Additionally, PARK2 negatively regulated OS development through the JAK2/STAT3/VEGF pathway. Our findings demonstrate that PARK2 is a tumor suppressor gene that may negatively affect OS growth and angiogenesis via partly inhibiting the JAK2/STAT3/VEGF signaling pathway.