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Objective: The Polygonatum cyrtonema was processed to investigated its effects on material and energy metabolism in CUMS depressed model mice. Methods: 80 KM/SPF mice were randomly divided into model group, positive group, processed P. cyrtonema group and compatible group, with male and female were equally divided. CUMS depressed mice model were established by unpredictable mild stress for 28 days. The levels of ICD, α-KGDHC, ATPs and Na+-K+ ATPase in brain, cerebellum, liver, kidney and spleen were detected by ELISA. Results: Processed P. cyrtonema and its compatibility had different effects on the enzyme levels of material and energy metabolism in both male and female mice. Compared to the positive group, each treatment group was affected significantly (P＜0.05). P. cyrtonema could significantly increase the α-KGDHC content in brain, cerebellum, liver, kidney and spleen of female mice (P＜0.01), and complex differences in levels of ICD α-KGDHC, ATPs and Na+-K+ ATPase in different organs of male and female mice were observed. Conclusion: Processed P. cyrtonema and its compatibility had different effects on the enzyme levels of marerial and energy metabolism in both male and female mice. P cyrtonema group had the strongest effect on depressed mice.