Structural Dissimilarity Sampling (SDS) is proposed as an efficient conformational search method to promote structural transitions essential for the biological functions of proteins. In SDS, initial structures are selected based on structural dissimilarity, and conformational resampling is repeated. Conformational resampling is performed as follows: (I) arrangement of initial structures for a diverse distribution at the edge of a conformational subspace and (II) promotion of the structural transitions with multiple short-time molecular dynamics (MD) simulations restarting from the diversely distributed initial structures. Cycles of (I) and (II) are repeated to intensively promote structural transitions because conformational resampling from the initial structures would quickly expand conformational distributions toward unvisited conformational subspaces. As a demonstration, SDS was first applied to maltodextrin binding protein (MBP) in explicit water to reproduce structural transitions between the open and closed states of MBP. Structural transitions of MBP were successfully reproduced with SDS in nanosecond-order simulation times. Starting from both the open and closed forms, SDS successfully reproduced the structural transitions within 25 cycles (a total of 250 ns of simulation time). For reference, a conventional long-time (500 ns) MD simulation under NPT (300 K and 1 bar) starting from the open form failed to reproduce the structural transition. In addition to the open-closed motions of MBP, SDS was applied to folding processes of the fast-folding proteins (chignolin, Trp-cage, and villin) and successfully sampled their native states. To confirm how the selections of initial structures affected conformational sampling efficiency, numbers of base sets for characterizing structural dissimilarity of initial structures were addressed in distinct trials of SDS. The parameter searches showed that the conformational sampling efficiency was relatively insensitive with respect to the numbers of base sets, indicating the robustness of SDS for actual applications.