Rhodnius neglectus is a potential vector of Trypanosoma cruzi (Tc), the causative agent of Chagas disease. The salivary glands (SGs) and intestine (INT) are actively required during blood feeding. The saliva from SGs is injected into the vertebrate host, modulating immune responses and favoring feeding for INT digestion. Tc infection significantly alters the physiology of these tissues; however, studies that assess this are still scarce. This study aimed to gain a better understanding of the global transcriptional expression of genes in SGs and INT during fasting (FA), fed (FE), and fed in the presence of Tc (FE + Tc) conditions. In FA, the expression of transcripts related to homeostasis maintenance proteins during periods of stress was predominant. Therefore, the transcript levels of Tret1-like and Hsp70Ba proteins were increased. Blood appeared to be responsible for alterations found in the FE group, as most of the expressed transcripts, such as proteases and cathepsin D, were related to digestion. In FE + Tc group, there was a decreased expression of blood processing genes for insect metabolism (e.g., Antigen-5 precursor, Pr13a, and Obp), detoxification (Sult1) in INT and acid phosphatases in SG. We also found decreased transcriptional expression of lipocalins and nitrophorins in SG and two new proteins, pacifastin and diptericin, in INT. Several transcripts of unknown proteins with investigative potential were found in both tissues. Our results also show that the presence of Tc can change the expression in both tissues for a long or short period of time. While SG homeostasis seems to be re-established on day 9, changes in INT are still evident. The findings of this study may be used for future research on parasite-vector interactions and contribute to the understanding of food physiology and post-meal/infection in triatomines.