Insects are known invertebrate species with economic, ecological, pathological, and medicinal value, as well as closely associated with human populations. Entomophagy and entomotherapy are future promising prospects largely attributable to the abundant availability, high protein content, and climatic sustainability of insects. In particular, the insect brain is an important system with a secluded, compact, and protective exoskeleton. It is immunologically privileged and capable of producing a robust immune response against pathogens. It is also a source of materials that initiate key activity throughout the body. Proteomic interrogation of Periplaneta americana enables understanding the role of this insect in the fields of food and pharmacology. Proximate analyses of P. americana highlights its richness in proteins. Here we perform a simple proteomic analysis to study the brain proteome of P. americana. The processes applied during the study include gel-based isolation and separation of proteins, followed by NanoLC-MS (Orbitrap) analyses and bioinformatic interrogation of the data. The results demonstrated that this insect proteome comprises antimicrobial proteins, allergens, and proteins required for metabolic processes.