The creep strength of Ag-based alloys can be remarkably enhanced through the formation of twin structures. In this study, the effects of alloying elements, including Sn, In, Zn, Cu, Zr, Ni, Ir, Cr, and W, on the formation enthalpy of point defects and the generalized stacking fault energy of Ag-based alloys were investigated using first-principles calculations. The formation enthalpy of point defects serves as a measure of the difficulty of alloying element doping in Ag-based alloys. Calculation results shows that the ability of alloying element doping to form point defects follows the order of Sn > In > Zn > Cu > Zr > Ni > Ir > Cr > W. The generalized stacking fault energy along the [112‾](111) slip direction in Ag-based alloys characterizes the competition between dislocation slip and twinning. As the formation enthalpy of point defects increases, the intrinsic stacking fault energy increases, leading to a decrease in twinning tendency. Once the formation enthalpy of point defects corresponding to the alloying element exceeds 1 eV, the intrinsic stacking fault energy and twinning tendency remain relatively unchanged. Comprehensive analysis shows that alloying elements Sn and In effectively reduce the intrinsic stacking fault energy and promote twinning, which aligns with the behavior observed in commonly used Ag–Sn–In electrical contact materials.