Termites are well-known for their status as major structural pests worldwide. Several major pest species rely on both symbiotic and endogenous cellulases for the digestion of cellulosic materials. This cellulase system is considered a potential target site for novel termite controlling agents. Thus, the main objective of this study was to identify novel compounds that target the termite cellulase system. Specifically, three prototype cellulase inhibitors were tested against workers of the Eastern subterranean termite, Reticulitermes flavipes, including the disaccharide-based cellobioimidazole (CBI) and fluoro-methyl cellobiose (FMCB) and the monosaccharide-based fluoro-methyl glucose (FMG). This study provides novel data indicating disaccharide-based inhibitors CBI and FMCB elicit feeding stimulation and termite mortality, and that all three compounds significantly inhibit cellulase enzymes after 24-day feeding bioassays.