Abstract. This paper introduces the sparsifying preconditioner for the pseudospectral approximation of highly indefinite systems on periodic structures, which include the frequency-domain response problems of the Helmholtz equation and the Schr¨odinger equation as examples. This approach transforms the dense system of the pseudospectral discretization approximately into a sparse system via an equivalent integral reformulation and a specially designed sparsifying operator. The resulting sparse system is then solved efficiently with sparse linear algebra algorithms and serves as a reasonably accurate preconditioner. When combined with standard iterative methods, this new preconditioner results in small iteration counts. Numerical results are provided for the Helmholtz equation and the Schr¨odinger in both two and three dimensions to demonstrate the effectiveness of this new preconditioner. Key words. Helmholtz equation, Schr¨odinger equation, preconditioner, pseudospectral approxima...