Low glycemic index (GI) food can be very necessary to alleviate the ever-increasing prevalence of diabetes, particularly for the high-quality living standards and health care services. Among them, the starch-lipid complexes can serve as a new type of resistant starch for excellent anti-digestive properties in recent years. High amylose corn starch (HACS) is considered an ideal raw material for the preparation of starch-lipid complexes, due mainly to the high amylose content. Meantime, the twin-screw extrusion has been successfully applied to fabricate the starch-lipid complexes. It is a high demand to enhance the preparation efficiency of starch-lipid complexes for scale production in anti-digestive food. The purpose of this study was to optimize the extrusion process for better structure and physicochemical properties of HACS-lipid complexes using single-factor and orthogonal experiments. Among them, the complex index (CI) was selected as the indicator. The high-amylose corn starch and flax oil were used as the material to prepare the complexes using twin-screw extrusion. The process parameters were adjusted separately, including the mass ratio, feed moisture, barrel temperature, and screw speed. The extruded complex was dried at 40 ℃ in an oven for 10 h, and then ground and passed through an 80-mesh sieve. The highest CI reached 85.63%, when the optimal parameters were 0.24 of flax oil-to-starch ratio, 40% of feed moisture, 125 °C of barrel temperature, and 150 r/min of screw speed. Fourier transform infrared spectroscopy (FTIR) pattern found the new peaks at 2 850 and 1 743 cm-1 in the extruded starch-lipid complex, corresponding to the C-H and C=O vibration absorption peak of lipid molecules in the complex. Moreover, the C=O vibration absorption peak of the extruded complex was shifted to the lower wavenumber, compared with the control. It infers that the lipid molecules combined with the starch were at the actions of shearing, friction force, and heat moisture during extrusion. Specifically, the extrusion first broke the hydrogen bonds of starch molecules to expose the hydrophobic helical cavity, where the lipid molecules were entered under hydrophobic interaction. The morphologies showed that the complexation induced the stacking and aggregation of starch granules. The V-type crystalline X-ray diffraction (XRD) pattern was found in the extruded complex, indicating the feasible preparation of the complexes after twin-screw extrusion. Compared with the control and HACS, there was a higher gelatinization enthalpy in the extruded complex, indicating that more energy was required to gelatinize the complex. By contrast, the extruded complex demonstrated a lower apparent viscosity, storage modulus, and loss modulus, compared with the control. Additionally, there was the highest total amount of slowly digestible starch (SDS) and resistant starch (RS) in the extruded complex among all samples, indicating the better anti-digestible properties of the complex. It can be concluded that the extrusion can promote the effective complexation between the starch and fax oil, thus altering the structure and physicochemical properties of corn starch. Therefore, the starch-lipid complex prepared by twin-screw extrusion can be expected to serve as a potential material for low GI food production.