Objective To explore the effects of Shaoyao Gancao granule on hair growth, behavior and hypothalamic pituitary adrenal (HPA) axis in mice with alopecia areata (AA). Methods Forty-two C3H/HeJ mice were randomly divided into control, model, Shaoyao Gancao granule, corticotropin-releasing hormone receptor 1 (CRHR1) antagonist, and compound glycyrrhizin tablet (CGT) group. Photography, dermoscopy photography, weight weighing, behavioral measurement were taken, as well as corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, glucocorticoid receptor (GR), and brain derived neurotrophic factor (BDNF) were assessed. Results Compared with the model group, high-dose Shaoyao Gancao granules could improve hair regeneration and weight gain (P<0.05), increase the percentage of total exercise distance and central area exercise distance in the open field experiment (P<0.05), reduce the immobility time in the forced swimming experiment and tail suspension experiment (P<0.05), reduce peripheral blood CRH, ACTH, Cortisol levels (P<0.05), and increase the expression of GR and BDNF in the hippocampus (P<0.05). Conclusions Shaoyao Gancao granule can promote hair growth and improve behavioral performance in mice with AA. The effects may be related to downregulating the levels of CRH, ACTH, and Cortisol, upregulating the expression of GR and BDNF, and inhibiting excessive activation of the HPA axis.