Design optimization of defense hole systems placed near the main circular cutout of composite laminated plates subject to biaxial loading is performed in this study. For that purpose, a numerical framework based on finite element models validated experimentally via RGB-photoelasticity and by reproducing selected cases available in literature is developed. Redesign optimization technique is utilized to reach the optimum geometric design parameters of the defense hole system, i.e., size and location. Parametric study for fiber orientation, biaxial loading ratio, stiffness ratio and stacking sequence is conducted as well. Stress concentration near circular cutouts can be reduced by 24.5%, 25.5%, 29.1%, 31.7% and 20.6% for values of the loading ratio equal to, respectively, 0, 0.25, 0.50, 0.75 and 1. Such significant reductions are obtained by introducing four elliptical defense holes along the principal stress direction lined up with fibers.