The lightweight Al3Ti intermetallic compound shows superior properties at elevated temperatures but its room-temperature brittleness largely limits its usefulness. We propose Al3Ti-based lightweight medium-entropy alloys (MEAs) with selected alloying elements, which change Al3Ti from a tetragonal D022 structure to a ductile cubic L12 one with embedded hard B2 and D8a phases. A combination of improved ductility and strength can be achieved. Four lightweight AlTiCrMnFeCu MEAs (ρ=3.65∼4.27 g/cm3) with tunable balance between hardness and ductility were fabricated. Ti and Fe promoted the formation of hard B2 phase, while Cr and Mn favored the formation of D8a phase which strengthened the alloy at the minor expense of ductility. The compressive yield and peak strengths of the MEAs e.g., Al55Ti20Cr5Mn10Fe5Cu5, can reach as high as 650 MPa and 1366 MPa, respectively, with its fracture strain around 17 %. This study provides useful information for designing Al3Ti-based lightweight MEAs with desirable properties.