A non-complete graph is \emph{$2$-distance-transitive} if, for $i=1,2$ and for any two vertex pairs $(u_1,v_1)$ and $(u_2,v_2)$ with the same distance $i$ in the graph, there exists an element of the graph automorphism group that maps $(u_1,v_1)$ to $(u_2,v_2)$. This is a generalization concept of the classical well-known distance-transitive graphs. In this paper, we completely determine the family of $2$-distance-transitive Cayley graphs over the generalized quaternion groups.