Objective Based on two different kidney-yang deficiency rat models induced by hydrocortisone and adenine, this study investigates the differential regulatory effects of Cervi Cornu Pantotrichum (CCP) on the HPG axis and the HPA axis. Methods Analysing the protein composition of CCP using LC-MS. Male SD rats were modeled with hydrocortisone and adenine, respectively, and the rats were monitored for physical signs, dietary changes, and mating and endurance behavioral studies, and sperm quality was observed after 6 weeks of CCP administration. Rat serum was assayed for cAMP, cGMP, T, E2, ACTH, CORT, CAT, MDA, IL-6, TNF-α, and so on. RT-PCR detection of gene expression levels for ADCY2, PKA, AC1, EDNRB, CCKBR, and other genes in the brain. Results The protein in CCP is primarily collagen. The hydrocortisone-induced Kidney-Yang deficiency model exhibited significantly greater regulatory effects on the HPA axis compared to the adenine model, manifested as adrenal cortex damage and reduced levels of ACTH and CORT hormones, thereby inhibiting midstream HPA axis function. In contrast, the adenosine-induced Kidney-yang deficiency model exhibited significantly greater regulation of the HPG axis than hydrocortisone, primarily through damage to HPG axis target organs leading to reduced sperm motility and diminished ACTH inhibition of upstream HPA axis regulation. CCP restores sperm motility by repairing testicular and adrenal cortical damage, promotes secretion of hormones such as T and ACTH, and significantly improves abnormal HPG/HPA axis regulation induced by both models. Additionally, CCP effectively modulates energy metabolism-related factors like cAMP and ameliorates adenosine-induced renal injury through alleviating renal fibrosis, restoring renal function, and exerting anti-inflammatory effects. The hydrocortisone model induces comprehensive downregulation of genes including ADCY2 in the brain, while the adenosine model simultaneously suppresses ADCY2, PKA, and AC1 expression while causing abnormal upregulation of EDNRB and CCKBR. CCP intervention specifically upregulates suppressed cAMP pathway genes in both models and selectively downregulates overexpressed EDNRB and CCKBR in the adenosine model, implying its multi-target mechanism in improving neuro-molecular disorders caused by different etiologies. Conclusion Hydrocortisone-induced Kidney-yang deficiency is primarily characterized by suppression of the HPA axis, while adenine-induced Kidney-yang deficiency mainly involves impairment of the HPG axis and damage to target organs. CCP can restore HPG/HPA axis function by repairing tissue structure and promoting hormone secretion. It also regulates the cAMP pathway, corrects abnormal expression of EDNRB and CCKBR in the adenine model, improves renal fibrosis and inflammation, and demonstrates comprehensive therapeutic effects, particularly in mitigating multi-system damage.