Thermoplastic polymers provide a versatile platform to mimic various aspects of physiological extracellular matrix properties such as chemical composition, stiffness, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of the most promising thermoplastic polymers, and in particular the thermoplastic polyesters, such as poly(lactic acid), poly(glycolic acid), and polycaprolactone, and the thermoplastic elastomers, such as polyurethanes, polyhydroxyalkanoates, and poly(butyl cyanoacrylate). A particular focus has been made on the synthesis processes, the processability and the biocompatibility. We also discuss how these materials can be applied in tissue engineering, mimicking tissues' structure and function, and stimulate mesenchymal stem cells differentiation and mechanotransduction.