With thrust weight ratio increasing, integral panel is an important component to reduce the aircraft weight, and it is a great challenge to ensure the forming accuracy and mechanical property in the large-scale panel. Laser shock forming has a great development prospect in realizing integral panel forming and improving its mechanical properties. This work investigated unequal alternate double-sided laser shock forming, which can make 7075 aluminum panel form and induce the hardened layers in both panel sides. The improvements were analyzed in mechanical properties and microstructure evolution of 7075 aluminum panels after unequal alternate double-sided laser shock forming. In the surface and subsurface layer, the residual stress and microhardness were verified to be enhanced by the laser shock wave. The results of XRD and EBSD provided the evidence of grain refinement. The strengthening mechanism of unequal alternate double-sided laser shock forming was analyzed in this work. The grains are distorted and refined during high strain rate plastic deformation due to dislocation slip and accumulation. The mechanical properties were enhanced by unequal alternate double-sided laser shock forming due to the hardened layers in both panel sides. The hardened layers and grain refinement have a great significance in inhibiting the crack generation and growth.