AbstractHerein, we explored the effects ofPoria cocosextract, protein powder mixture, and their combined intervention on weight loss in high‐fat diet (HFD)‐induced obese mice. Male C57BL/6J mice were selected and fed a HFD for 8 weeks; obese mice that were successfully modeled were divided into modeling and five intervention groups, and given the corresponding treatment for 10 weeks. Body weight, fat, and muscle tissue, blood glucose, lipids, inflammatory factors, and other glucose and lipid metabolism‐related indicators were measured to evaluate the effect ofP.cocosand protein powder intervention on weight loss in obese mice. The body weight of the intervention group was reduced compared with the HFD group. Fat content of mice in F3PM group decreased significantly (p< .05). Levels of blood glucose, lipids, adiponectin, leptin, and inflammatory factors, including interleukin‐1 β and tumor necrosis factor‐ α showed improvement. Lipoprotein lipase (lower about 2.97 pg/ml, vs. HFD mice 10.65 mmoL/ml) and sterol regulatory element‐binding transcription factor (lower about 1413.63 pg/ml, vs. HFD mice 3915.33 pg/ml) levels in liver tissue were decreased. The respiratory exchange rate (RER) of mice in the HFD and subject intervention groups had no circadian rhythm and was maintained at approximately 0.80. The protein powder mixture (PM) group had the lowest RER (p< .05), theP.cocosextract (FL) and F1PM groups had similar RER to the HFD group (p< .05), and the F2PM group had a higher RER than the HFD group (p< .05). And food intake and energy metabolism returned to circadian rhythm, with an increase in the dose ofP.cocosextract, the feeding rhythms of F1PM, F2PM, and F3PM were closer to that of the normal diet (ND) group. Feeding intervention withP.cocosand protein powder improved fat distribution, glucolipid metabolism, and energy metabolism, with the combination of F3PM showing more diverse benefits.