Poly lactic-co-glycolic acid (PLGA), a synthetic polymer, belongs to the fabrication of poly(α-hydroxy acid) systems approved by the US Food and Drug Administration. PLGA has been widely used in clinical applications due to its excellent biocompatibility, controlled biodegradability, and convenient processability. However, their degradation products cause inflammation, their rate of hydrolysis is slow, and the release rate of the drug is delayed. Therefore, polyoxalate (POX), which is a biodegradable polymer, was used to overcome these problems. The amount of POX was gradually increased to reduce the toxicity of PLGA, and the degree of cell proliferation was confirmed. In this study, POX/PLGA film in different composition was prepared and they were characterized using scanning electron microscope (SEM). Fourier-transform infrared spectroscopy (FTIR), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and real-time polymerase chain reaction (RT-PCR). Among the different combination studied, 50% POX/PLGA film showed better results for all the analyses performed compared with other scaffolds, when the National Institute of Health (NIH)/3T3 mouse embryo fibroblasts were cultured in vitro. We confirmed that 50% POX/PLGA film can be applied in different tissue engineering fields including bone tissue engineering and drug delivery applications.