The emerged strategy of entropy engineering provides new ideas for realizing high-performance thermoelectric materials, but it is still much unresolved how to achieve delicate trade-off between the carrier mobility m H and the lattice thermal conductivity κ ph in taking advantage of configurational entropy ΔS. Herein, the significant advances of ultralow κ ph yet decent m H in a new medium-entropy system of well-designed (Pb, Ge, Sb, Cd) co-alloyed SnTe is reported. Moreover, the co-alloying also optimizes the carrier concentration n H and promotes the valence band convergence, thereby yielding an excellent Seebeck coefficient and compensating for decreased electrical conductivity. Consequently, a high peak ZT of 1.5 at 800 K, a record average ZT of 0.84 (300−800 K), and a remarkable Vickers hardness of 134 H V are concurrently attained in Cd 0.02 (Sn 0.59 Pb 0.15 Ge 0.2 Sb 0.06 ) 0.98 Te. Benefiting from the synergistically increased ZT and mechanical strength, the fabricated 17-couple SnTebased thermoelectric module exhibits a competitive conversion efficiency of 6.3% at ΔT = 350 °C. This study not only provides a paradigm of the medium-entropy design for thermoelectric materials but also puts forward an innovative scheme for low-grade heat harvest by SnTe-based TE module.