The desert-dwelling Cistanche herb was first recorded in the “Shen Nong Herbal Classic” and is listed as the top-grade herbal medicine in this publication. The Chinese Pharmacopoeia records that pieces of Cistanche deserticola (CD) and rice wine-steamed Cistanche deserticola (WCD) can be used in the clinic as the main types of decoctions. After being steamed with rice wine, the antiaging and tonifying kidney-yang effects are enhanced. In this study, we detected the chemical content of CD and WCD and the pharmacological mechanism of invigorating kidney-yang deficiency in model rats. Aim. The purpose of this study was to examine the effects of CD and WCD on the neuroendocrine-immune function of kidney-yang deficiency in glucocorticoid-overdosed model rats. Materials and methods. Sprague Dawley (SD) rats were selected. The rats were subcutaneously injected with corticosterone water suspension for the glucocorticoid-overdosed model rats. The positive control rats were gavaged with Jinkuishenqi pills and high-, medium-, and low-dose CD/WCD suspensions (1.646 g/(kg day), 5.48 g/(kg day), 2.74 g/(kg day), and 1.37 g/(kg day), respectively); the blank control (BC) and model control (MC) groups were given the same volume of distilled water as those in the drug group for 40 consecutive days at a dose of 1 mL/100 g. After the last administration, the blood was collected from the abdominal aorta, and serum levels of T, CRH, ACTH, CORT, cortisol, IL-10, IL-6, IL-2, TNF-α, and IFN-γ were measured. Organ indexes of the thymus gland and the spleen were calculated. The expression of Bax, Bcl-2, caspase-3, Fas, and FasL in the adrenal gland was measured by immunohistochemistry. The pathological changes in the thymus gland and the adrenal gland were observed by HE staining (×200). T lymphocyte subsets in peripheral blood were detected by flow cytometry, and the expression of CaM mRNA in the hypothalamus and hypophysis tissues was also measured by RT-PCR. Results. Compared with the MC group, the CD and WCD groups exhibited increases in activity, the organ index of the thymus and the spleen, the serum levels of T, CRH, ACTH, CORT, cortisol, IL-2, and IL-10, the ratio of CD4+/CD8+, and the expression of Bcl-2, caspase-3, Fas, FasL, and CaM in the hypophysis tissue. The CD and WCD groups also exhibited reductions in the IL-6, TNF-α, and IFN-γ levels in serum and the expression of CaM mRNA in the hypothalamus. Conclusions. Each dose of CD and WCD could counteract the dysregulated sex hormone and immune factors in glucocorticoid-overdosed model rats, enhancing and restoring the effect of the hypothalamic nerve cells and improving immune function.