Timber structures are susceptible to sound propagation problems. The issue can be mitigated by decoupling structural components at connections level by means of polyurethane soundproofing interlayers. These layers are much softer than timber but, at the same time, they are characterized by higher friction coefficients. In this paper, an experimental investigation is carried out to characterize the mechanical behavior of insulated screw connections assessing the implications of the soundproofing layer use. Different interlayers, screw inclination angles and setups are considered. The load–slip behavior is studied, and a proper empirical model, suitable for performing push-over analysis of buildings involving soundproofed connections, is derived. The essential design parameters, namely the slip modulus, the strength and ductility, are determined and compared with existing models predictions, thus testing their accuracy. Substantial reductions in terms of stiffness, load-carrying capacity and ductility are observed in soundproofed connections.