AbstractBiodegradable blends of polylactic acid (PLA) and thermoplastic starch (TPS) co‐plasticized with glycerol (G) and isosorbide (i) in different ratios were prepared by extrusion in a single screw extruder. The G/isosorbide ratio varied within the range 27.5/2.5 to 15/15. The resulting materials were obtained through blown film extrusion and characterized using a variety of techniques. The plasticizing effect was identified through SEM and FTIR observations. In the SEM images, it was evident that most of the native crystalline structures were destructured. Furthermore, SEM observations showed phase separation of TPS and PLA in all samples, with phase dispersion differences depending on the co‐plasticizer ratio. The FTIR spectra of all TPS/PLA films showed that isosorbide caused changes in the absorption bands that suggested a reduction in the crystallinity of the native starch, agreeing with the XRD results that indicated the formation of different crystalline structures (EH type). The XRD results revealed a change in the crystal structure of the TPS phase influenced by the amount of isosorbide. Isosorbide increased tensile strength and reduced elongation due to strong interactions between the plasticizer and the starch chains through hydrogen bonds, con‐firmed by FTIR analysis. In general, it was established that isosorbide and G co‐plasticization, with small amounts of isosorbide (up to a ratio of 25:5 G/isosorbide), can be employed as an effective plasticizer without significantly affecting the tensile mechanical properties.