This chapter explores the versatile application of the silkworm (Bombyx mori) expression system for producing a wide array of complex recombinant proteins. It details advanced strategies to enhance the yield and proper folding of secretory proteins, specifically highlighting the integration of the bombyxin signal sequence into the BmNPV bacmid and the coexpression of molecular chaperones, such as BiP and calnexin, to mitigate aggregation and improve cellular secretion. Furthermore, the chapter demonstrates the successful expression of challenging membrane proteins while maintaining their functional conformations. A major focus is placed on the generation of highly immunogenic virus-like particles (VLPs), detailing the production of both enveloped (eVLPs) and nonenveloped (neVLPs) structures suitable for vaccine development. To address downstream processing bottlenecks, the chapter presents systematic, scalable purification protocols tailored specifically for silkworm-derived eVLPs and neVLPs, ensuring high purity, structural integrity, and biological activity. Collectively, these technological advancements underscore the silkworm’s efficacy as a robust, high-yield biofactory for the scalable production of therapeutically relevant glycoproteins, membrane receptors, and macromolecular viral assemblies.