Insects, especially crickets, have been proposed as a novel source of nutrients in human nutrition since they possess bioactive molecules, including high protein content, lipids, chitin, vitamins and minerals. In this work, the nutritional and functional properties of a novel Italian spray-dried (SD) cricket powder were evaluated. The powder was characterized by physico–chemical properties (morphology, size distribution, solid state, thermal profiles, and surface zeta potential), and antioxidant properties. Moreover, preclinical properties (cytocompatibility and pro-inflammatory immune response) were assessed. The powder was characterized by microparticle structure with bulges and rough surfaces, showing distinctive antioxidant properties. The preclinical results suggested that the SD crickets were biocompatible towards Caco-2 and macrophages without immune response, representing an interesting material for the food industry that could provide health benefits in addition to the basic nutritional value of traditional foods.