In this work, we report a comparative study of the interfacial properties of fcc-Al/L12-Al3M (M = Sc, Ti, V, Y, Zr, Nb) from first-principles calculations. It is found that the fcc-Al(111)/L12-Al3Nb(111) interface is energetically favorable because of its negative interfacial energy (-0.225 J m-2), whereas the interfacial energies of the other five interfaces are positive. Despite their thermodynamically unfavorable characteristics, the stabilities of the formed interfaces are ranked in the order fcc-Al(111)/L12-Al3Nb(111) > fcc-Al(111)/L12-Al3Ti(111) > fcc-Al(111)/L12-Al3Zr(111) > fcc-Al(111)/L12-Al3Sc(111) > fcc-Al(111)/L12-Al3V(111) > fcc-Al(111)/L12-Al3Y(111). Moreover, the computed generalized stacking fault energy curves revealed that the (111)[11-2] slip system is preferred over the (111)[10-1] slip system under external stresses for all six interfaces. Based on the Rice ratio criterion, the interface slips also energetically favor the generation of stacking faults instead of cleavage for these interface systems; this finding implied that these interfaces did not greatly influence the plastic deformation behavior of aluminum. Furthermore, the derived bulk elastic properties indicate that fcc-Al, L12-Al3Nb, and L12-Al3V tend to present ductile behavior, while L12-Al3Zr, L12-Al3Ti, L12-Al3Y, and L12-Al3Sc are found to be brittle compounds. Nevertheless, all of these intermetallics can strengthen the aluminum matrix without losing much plasticity to provide a higher elastic modulus than aluminum along with the ductile interface nature of fcc-Al(111)/L12-A13M(111).