Topological insulators and semimetal materials composed of heavy elements usually have inverted and dispersive band structures. It is interesting to notice that if lighter elements with reduced spin-orbit coupling are substituted for the heavy elements, the topological materials can be mutated into semiconductors with variable band gaps; for example, topological HgTe and Bi2Se3 can be mutated into CdTe and Sb2Se3, which are excellent optoelectronic semiconductors because the element substitution opens the band gap and meanwhile inherits the large band dispersion and high carrier mobility. Recently, many topological materials have been reported, and their databases have been built. Here, we demonstrate that these new topological materials can be used as the starting points to search for semiconductors with high carrier mobility and defect tolerance through element substitution. We take three recently discovered topological materials, Na3Bi, Pb2Bi2Te5, and EuCd2Sb2, as the benchmark systems to show the general validity of this strategy and find that the derived Na3P, Na3As, Sn2Sb2S5, and CaZn2N2 are all band-dispersive and defect-tolerant semiconductors with potential optoelectronic applications. For Na3P, Na3As, and Na3Sb, the new P3̅c1 structure derived from the topological Na3Bi is found unexpectedly to be their ground-state structure, more stable than their well-known structures reported in the literature. This study not only gains new insights into the physical properties of these semiconductors but also proposes an effective strategy for the search of band-dispersive and defect-tolerant semiconductors that can be generalized to other topological materials.