Background. The theories of Shen-reinforcement and Qi-supplementation are important in asthma treatment based on traditional Chinese medicine theories. Early studies suggested that Invigorating Kidney and Supplementing Qi herbal formulae, Bu Shen Fang Chuan (BSFC) and Bu Shen Yi Qi (BSYQ), conveyed promising results in asthma treatment. However, the efficacy and safety of the formulae need to be further investigated by a randomized double-blind clinical trial. Methods. 328 eligible patients were randomly sent to BSFC, BSYQ, and placebo group. The two formulae were received as add-on therapy. The primary endpoints were rate of asthma exacerbation and Hamilton Rating Scale for Depression (HAM-D) score. The secondary endpoints included HPA axis function and inflammatory cytokine production profile. All indexes were measured before and after treatment. Results. The primary endpoints were not improved in both groups; however, the depression levels of subgroup patients with HAM-D score > 5 were improved in BSFC group. HPA axis functions and inflammatory cytokines level were also improved by two formulae. The incidences of adverse events were similar among groups. Conclusions. The two formulae had multiple advantage effects on neuroendocrine-immune system. They are worth used as a replacement therapy in asthma. Trial Registration. This trial is registered with clinical trial number ChiCTR-PRC-09000529.