The multiplicity-free subgroups (strong Gelfand subgroups) of wreath products are investigated. Various useful reduction arguments are presented. In particular, we show that for every finite group $F$, the wreath product $F\wr S_λ$, where $S_λ$ is a Young subgroup, is multiplicity-free if and only if $λ$ is a partition with at most two parts, the second part being 0,1, or 2. Furthermore, we classify all multiplicity-free subgroups of hyperoctahedral groups. Along the way, we derive various decomposition formulas for the induced representations from some special subgroups of hyperoctahedral groups.