The vibration-reduction and sound-absorption properties of a truss-core sandwich beam are analyzed. The core is composed by the assembly of unit cells across both the length and thickness of the proposed beam. The cells have chiral geometry which features cylinders, or nodes, joined by ligaments, or ribs. The resulting assembly is characterized by a number of interesting properties that can be exploited for the design of alternative honeycomb or cellular topologies to be used in sandwich construction. The vibro-acoustic analysis of the considered beam is performed through a finite element model developed using a commercially available Finite Element package. In the model, the sandwich beam is constrained to a rigid baffle and divides two fluid domains of infinite extent. The dynamic performance of the beam is evaluated through the estimation of the vibration amplitudes of the two constraining layers, while the performance of the beam as an acoustic panel with high insulation characteristics is analyzed through the estimation of the sound transmission loss between the two fluid domains. A sensitivity study to investigate the influence of core configuration and geometry on the beam’s performance is presented. The results indicate the design flexibility offered by the proposed design, which allows modifying and optimizing the structural acoustic performance of the beam through proper selection of the core configuration.