In this study, an optimized composite was prepared based on chemically modified corn straw, chitosan, and poly(lactic acid) using Response Surface Methodology (RSM). The composite was produced by screw extruding and hot pressing. The Box Behnken Design (BBD) software was used to design the test to optimize the composite composition. The optimum ratio of 3 factors, e.g. chemically modified corn straw (0.10 to 0.40 g), chitosan (0.25 to 0.75 g), and poly(lactic acid) (2.00 to 3.00 g) on the response value (bending strength) of the composite was investigated. RSM-BBD provided the optimum combination of composites. The novel composite prepared under the optimized factors was characterized by Fourier transform infrared spectroscopy, mechanical testing, water absorption tests, contact angle tests, and scanning electron microscopy. The results showed that the mechanical strength, e.g., bending strength, impact strength, and tensile strength of chemically modified corn straw based composite were 21.6 MPa, 4.43 kJ/m2, and 20.0 MPa, respectively, which increased by 23.5%, 13.9%, and 18.7% compared to native corn straw based composite. Improved mechanical strength and hydrophobicity for chemically modified corn straw/chitosan/poly(lactic acid) demonstrated that chemically modified biomass fibers and bio-based degradable polymers have the potential to produce environmentally friendly composites.