Objective To explore the effects of Shaoyao Gancao granule on hair growth, behavior, and the 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 high-, middle-, low-dose, corticotropin-releasing hormone receptor 1 ( CRHR1) antagonist, and compound glycyrrhizin tablet ( CGT) groups. Photography, dermoscopy, weight analysis, and behavioral measurement were performed. Corticotropin-releasing hormone ( CRH ), adrenocorticotropic hormone (ACTH), cortisol, glucocorticoid receptor ( GR), and brain-derived neurotrophic factor ( BDNF) were also assessed. Results Compared with the model group, high-dose Shaoyao Gancao granules improve hair regeneration and weight gain (P<0. 05), increased the percentage of total exercise distance and central area exercise distance in an open field test (P<0. 05), reduced the immobility time in the forced swimming and tail suspension experiments (P<0. 05),reduced peripheral blood levels of CRH, ACTH, and cortisol (P<0. 05), and increased expression of GR and BDNF in the hippocampus ( P<0. 05 ). Conclusions Shaoyao Gancao granule promotes hair growth and improves behavioral performance in mice with AA. These effects may be related to downregulating CRH, ACTH, and cortisol expression, upregulating GR and BDNF expression, and inhibiting excessive activation of the HPA axis.