Colorado potato beetle, Leptinotarsa decemlineata (Say), is an important pest of potato throughout the world. Here, the effects of six potato cultivars including ‘Arinda,’ ‘Sprit,’ ‘Markiez,’ ‘Lotta,’ ‘Santae,’ and ‘Agria’ were studied on nutritional indices, digestive enzymes, and some components involved in intermediary metabolism of L. decemlineata. Nutritional indices of the larvae and the adults were significantly different followed by feeding on various potato cultivars. The individuals fed on Agria showed the highest activity of digestive proteases although cathepsin B demonstrated same Activity on Santae and Lotta. The highest activity of α-amylase was found in the larvae fed on Arinda, but the adults demonstrated the highest amylolytic activities on Santae and Agria. Both larvae and adults of L. decemlineata fed on Santae revealed the highest α- and β-glucosidase activities. No significant differences were found in lipase activity of larvae, but the highest lipase activity was found in the adults fed on Santae. The highest activities of transaminases were found in the larvae and adults fed on the Agria except for γ-glutamyl transferase. In case of aldolase, the highest activities were observed in the larvae and adults fed on Santae and Sprit. The highest activities of lactate dehydrogenase were obtained in the larvae and adults fed on Santae. The highest amount of low-density lipophorin was measured in both individuals fed on Santae. There were no significant differences in high-density lipophorin amount of adults, but the highest value was found in the larvae fed on Agria. The lowest amounts of protein and triglyceride were observed in both individuals fed on Santae and Agria, respectively. These results revealed Santae is the most suitable cultivar for L. decemlineata based on digestion and intermediary metabolism findings, but Lotta is an unsuitable cultivar and could be considered for integrated pest management.