Orthopedic implants are an important tool in the treatment of musculoskeletal conditions and helped many patients to improve their quality of life. Various inorganic-organic biocomposites have been broadly investigated particularly in the area of load-bearing orthopedic/dental applications. Polyimide (PI) is a promising organic material and shows excellent mechanical properties, biocompatibility, bio-stability, and its elastic modulus is similar to human bone but it lacks bioactivity, which is very important for cell adhesion and ultimately for bone regeneration. In this research, tantalum pentoxide (Ta2O5) coating was prepared on the surface of PI by polydopamine (PDA) bonding. The results showed that Ta2O5 was evenly coated on the surface of PI, and with the concentration of Ta2O5 in the PDA suspension increased, the content of Ta2O5 particles on the surface of PI increased significantly. In addition, the Ta2O5 coating significantly increased the roughness and hydrophilicity of the PI matrix. Cell experiments showed that PI surface coating Ta2O5 could promote the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived stromal cells (BMSCs). The results demonstrated that fabricating Ta2O5 coating on the surface of PI through PDA bonding could improve the biocompatibility as well as bioactivity of PI, and increase the application potential of PI in the field of bone repair materials.