Background: Herba Cistanches (Roucongrong) is effective in treating Shenxu Zheng ('kidneydeficiency syndrome'). However, the mechanisms and systemic metabolic responses to the herbal intervention are unclear. Methods: Using GC-MS-based metabolic profiling, we investigated the metabolic responses to Herba Cistanches intervention in a rat model of the hydrocortisone-induced 'kidney-deficiency syndrome'. Results: The metabolic profiles of the rats after hydrocortisone injection deviated from the predose metabolic state at different time points, ranging from day 1 to day 10, whereas the metabolic profiles of the rats treated with both hydrocortisone and water extract of Herba Cistanches returned to the pre-dose state on day 10. Conclusion: The intervention of Herba Cistanches caused a systemic recovery from the hydrocortisone-induced metabolic perturbation in rats. This study also demonstrates that metabolic profiling is useful in studying therapeutic mechanisms of herbal medicines.