Abstract: Hepatic osteodystrophy is one of the metabolic skeletal diseases, characterized by global changes in bone mineral density in patients with chronic liver disease (CLD) under osteomalacia and osteoporosis. It is often overlooked the complication in patients with CLD. Hepatic osteodystrophy can seriously affect the quality of life and long-term prognosis of the patients. In this study, five kinds of fruits and vegetables (including cerasus humilis, kiwifruit, carrot, grape, and orange) were used as the raw materials to prepare a composite solid beverage (hereinafter referred to as "Wuguo Powder") by spray drying. Then, the female C57 mice were fed with the Wuguo powder, in order to determine the serum indexes and the bone microstructures. A systematic investigation was made to clarify the preventive effects of Wuguo Powder on the hepatic osteopathy induced by high-fat diet. The basis was also offered for the production and the nutrition health function of the Wuguo Powder. The results showed that the optimal formula for five kinds of fruits and vegetables was 40% cerasus humilis, 20% kiwifruit, 20% carrot, 10% orange, and 10% grape. The ingredients were added 40% of the total soluble solids composite drying agent (maltodextrin: WPI=30:10) and 3% of the stabilizer sodium carboxymethyl cellulose (CMC). The spray drying conditions were obtained: the air temperature of entry was 126°C, the feed rate was 6.3 mL/min, the height of the rotameter was 44.00mm, and the soluble solid content was 11.00%. The powder collection rate of Wuguo Powder was 60.86% under these conditions. The serum test showed that the levels of OC and TRACP-5b in the serum of the mice in the administration group were significantly lower than those in the model group (P<0.05). The levels of SOD and GSH-Px were significantly higher than those in the model group (P<0.05), while the levels of MDA were significantly higher than those in the model group (P<0.05), whereas, the lower than that in the model group (P<0.05). The ALT and AST levels were significantly lower than that in the model group (P<0.05), indicating no significant difference, compared with the blank group (P>0.05). The TC, TG, LDL-C levels were significantly lower than that in the model group (P<0.05). The level of HDL-C was significantly higher than that in the model group (P<0.05), indicating no significant difference from the blank group (P>0.05). The Micro-CT showed that the femoral BMD, BV/TV, BS/TV, Tb.N, and Conn.D of the administration group significantly increased (P<0.05), compared with the model group, whereas, the BS/BV and Tb.Sp significantly decreased (P<0.05). The results showed that five fruit powders were prepared by spray drying using the cerasus humilis, kiwi fruit, carrot, orange, and grape as the raw materials, adding the maltodextrin, whey protein isolate (WPI) as a composite drying agent and stabilizer CMC. Five kinds of fruit-vegetable complex solid drinks regulated bone metabolism. Specifically, the levels of OC and TRACP-5b decreased in the serum, and the oxidative stress was improved by the decreasing content of MDA and the increasing levels of SOD and GSH-Px in the serum. The liver damage was relieved by the decreasing levels of ALT and AST in the serum, and the blood lipid metabolism was regulated by the decreasing levels of TG, TC, LDL-C in the serum and the increasing level of HDL-C in the serum. As such, the bone microstructure was improved by increasing BMD, BV/TV, BS/TV, Tb.N, and Conn.D value, while decreasing BS/BV, and Tb.Sp. Therefore, five kinds of fruit-vegetable complex solid drinks can be expected to serve as the better preventive effect on the hepatic osteopathy induced by a high-fat diet in mice.