Composites synthesized from natural waste and recycled plastic is quite a promising and interesting field for scientists and polymer industries. In the present study, bio-composites based on agriculture residue Sesamum indicum L. and recycled-low density polyethylene were synthesized by extrusion and injection molding technique at a fiber loading of 10–40 wt%. Additionally, 3% of maleic anhydride grafted low density polyethylene was used as a compatibilizer. The prepared composites were irradiated at 25 kGy, 75 kGy and 125 kGy doses of gamma rays. The effects of different fiber content and gamma doses on mechanical properties were studied statistically by Design Expert software. Response surface methodology was employed to depict the interaction among various factors and optimization was done by desirability index method. Findings indicated that composites having 30% Sesamum indicum L. irradiated at 125 kGy demonstrated best mechanical properties. A significant enhancement in tensile and flexural properties of irradiated composites can be explained effectively in terms of the cross-linking effect. The fiber–matrix adhesion and modifications in composite structure was characterized by fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and X-Ray diffraction (XRD) analysis. Furthermore, thermal stability of the composites was also found to be increased. In addition, gamma-irradiated composite exhibited the highest storage modulus and a decrease in mechanical loss factor was also observed.