The pathogen's effectiveness may be influenced by the insect's host plants. The purpose of this study was to examine if the entomopathogenic bacteria Bacillus thuringiensis var. kurstaki (BtK) was compatible with three hosts from diverse plant families including corn (Zea mays L.), lettuce (Lactuca sativa L.) and sugar beet (Beta vulgaris L.) against Spodoptera littoralis (Boisduval). BtK showed highest toxicity toward the sugar beet population compared with other host populations. The LC50 values of BtK were 17.67- and 7.89-fold for corn and sugar beet populations, respectively, lower than those of lettuce population. Because the difference might be explained by the dietary effects of host plants on the overall physiological condition of S. littoralis larvae, the digestive enzymatic and intermediate metabolism were investigated. The alpha-amylase and lipase activities in the midgut of S. littoralis lettuce population were all significantly higher than those of corn and sugar beet populations, while the highest activity of protease was observed in the corn population. In the lettuce population, the intermediary metabolism response, expressed as acid and alkaline phosphatases (ACP and ALP), was significantly (P <= 0.05) lower than those of the sugar beet and corn populations. On the contrary, the activity of lactate dehydrogenase (LDH) significantly increased on lettuce population compared with other host plants. The highest amount of protein (0.188 mg) and triglyceride (TAG: 0.219 mg/mL) was found in larvae fed on lettuce. According to these findings, the host plant has an indirect role in BtK's suppression of cotton leafworm.