Objective To investigate the effects of force on mechanical stability of FLNa-Ig21/αIIbβ3-CT complex and the regulation mechanism. Methods The FLNa-Ig21/αIIbβ3-CT crystal structures were taken from the PDB database. The stability of the complexes in a physiological environment as well as the unfolding path and mechanical stability induced by mechanical forces were analyzed using equilibrium and steered molecular dynamics simulations. Results During the equilibration, the survival rate of most salt bridge and hydrogen bonds was below 0.5, and the interactions between FLNa-Ig21 and αIIbβ3-CT was relatively weak. During stretching at a constant velocity, the complex could withstand a tensile force of 70–380 pN, and its mechanical strength depended on the force-induced dissociation path. Under a constant force of 0–60 pN, the complexes exhibited a slipping-bond trend, and the force increase facilitated the breakage of the R995-D723 salt bridge and the activation of αIIbβ3 integrin. Conclusions The force-induced allostery of αIIbβ3-MP enhanced the complex mechanical strength and delayed FLNa-Ig21 dissociation from αIIbβ3-CT. After the 20 pN threshold was exceeded, tensile force positively regulated the activation of αIIbβ3 integrin. These results provide references for further revealing the molecular mechanism of IIbβ3 integrin activation and related targeted drug development.