A variety of glycosylated and unglycosylated saponins from seven different plant families (Aquifoliaceae, Asparagaceae, Caryophyllaceae, Dioscoreaceae, Leguminosae, Rosaceae, Sapindaceae) were tested against the corn earworm, Helicoverpa zea, and the fall armyworm, Spodoptera frugiperda. The corn earworm feeds readily on both monocots and dicots, while the fall armyworm is primarily a grass feeder. Most of the saponins were similarly effective or ineffective against both insect species, with the glycosides being the primary active form (compared to aglycones). However, one aglycone possessed antifeedant properties toward the fall armyworm. Thus, in contrast to many plant secondary metabolites effective against either of these two species where the aglycone is more effective, in the case of the saponins the opposite is generally true. This appears to be a contradictory strategy of plant defenses that requires further consideration. The activity of protodioscin against insects is reported for the first time and may be important in insect defense by the bioenergy crop switchgrass.