In this paper, the problem of the self-adjointness for the case of a quantum mini-superspace Hamiltonian retrieved from a Brans-Dicke action is investigated. Our matter content is presented in terms of a perfect fluid, onto which Schutz’s formalism will be applied. We use the von Neumann theorem and the similarity with the Laplacian operator in one of the variables to determine the cases where the Hamiltonian is self-adjoint and if it admits self-adjoint extensions. For the latter, we study which extension is physically more suitable.