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A new design method of Al-Si-Mg alloy manipulated by in situ nanosized crystals was proposed. Starting from source design of the microstructure manipulation agent with a high crystallographic matching relationship with the α-Al, eutectic Si and Mg 2 Si phases in Al-Si-Mg alloy, the interatomic misfit (f r) between NiTi(B2) and α-Al or Mg 2 Si is 5.0% or 5.3%, respectively, and that between NiTi(B2) and Si is 9.9%, corresponding to good crystallographic matching. Based on calculations, in situ nanosized crystals could be considered as heterogeneous nucleation sites of α-Al, eutectic Si and Mg 2 Si, thus, uniformly fine α-Al grains, near-spherical eutectic Si and fine precipitated Mg 2 Si were obtained. The solidification behavior analysis also highly corresponded to the E2EM calculations. In the alloy manipulated by 0.05 wt% NiNbTi manipulation agent, the average sizes of α-Al, eutectic Si and Mg 2 Si were greatly decreased by nearly 8, 2 and 20 times, respectively, thus achieving comprehensive multiscale manipulation of the microstructure of the alloy in one step. Specially, the huge energy stemmed from the B2 to B19' phase transformation will generate a large number of crystal defects, which provides nucleation sites and driving force for the formation of Mg 2 Si and greatly refines the Mg 2 Si.Moreover, the yield stress, tensile stress and fracture strain of the manipulated alloy were simultaneously improved by 34.1%, 20.4% and 35.0%, respectively. The excellent strength and plasticity could be ascribed to grain-refinement strengthening, Orowan strengthening and eutectic Si refinement and spheroidization, which reduced the stress concentration during deformation. The comprehensive microstructure manipulation of Al-Si-Mg alloy using nanosized crystals formed by in situ physical crystallization, especially the manipulation of the precipitated phase, is an innovative work that not only avoids the "poisoning" effect between multiple manipulation agents but also realizes comprehensive manipulation of the overall microstructure, consequently broadening further industrial applications. • The low fr shows good mismatch between Al, Si, Mg 2 Si and NiTi. • The new method achieves multiscale manipulation of the alloy in one step. • The mean sizes of α-Al, eutectic Si and Mg 2 Si were decreased by nearly 8, 2 and 20 times. • The yield strength and plasticity were simultaneously improved by 34.1% and 35.0%. [ABSTRACT FROM AUTHOR]