Traditional Chinese Medicine Constitution (TCMC) divides human beings into balanced (ping-he) constitution (PH) and unbalanced constitution. Yang-deficiency (yang-xu) constitution (YAX) is one of the most common unbalanced constitutions in Chinese general population, and it causes susceptibility to particular diseases. However, unbalanced constitutions can be regulated by Chinese medicine and lifestyle intervention in clinical practice. Gui-fu-di-huang-wan (GFDHW) is a well-known Chinese medicine with yang-invigorating activity and is regarded as improving YAX. In this study, 60 healthy YAX students selected from a prospective population of 5185 were enrolled in a randomized clinical trial and completed the study. We compared the gut microbiota and urinary metabolome between individuals with PH and those with YAX before and after one-month-intervention. Compared with the control group, the health status of the intervention group improved significantly, the YAX symptom score was reduced, and the efficacy remained high at the one-year follow-up. The gut microbiota of the healthy PH exhibited greater diversity, and significantly higher species were identified.[Formula: see text]Compared to PH group, YAX individuals showed increased abundance of Bacteroidetes and Bacteroides,also had higher levels of gut microbial-derived urinary metabolites. After one-month-intervention, both GFDHW treatment and lifestyle intervention enriched the diversity and modulated the structure in YAX. The intervention group also partially restored the microbiome and metabolome to healthy PH-like levels. Further, a microbiota co-occurrence network analysis showed that the metabolites enriched in YAX were correlated with microbial community structure. Taken together, our results suggest that Chinese medicine combined with lifestyle intervention benefits YAX individuals. Gut microbiota/metabolite crosstalk might be involved in the Chinese medicine-mediated effects.