Although topical minoxidil is the most common drug for alopecia areata (AA), it has limited therapeutic effect in the treatment of patients with moderate and severe AA because it can only promote hair follicle growth and improve the characteristics of hair follicle degeneration in AA and cannot alleviate local inflammatory response. Therefore, we designed a novel topical compound gel loading minoxidil and Janus kinases (JAK) inhibitors tofacitinib. The compound gel not only had good semi-solid properties and the effect of permeation but also maintained stability for up to 3 months under accelerated conditions, ensuring the long-term quality of the formulation. This compound gel can effectively improve hair follicle growth and significantly alleviate local inflammatory response by downregulation of the ratio of inflammatory factor interferon-γ to anti-inflammatory factor interleukin-4 in C3H/HeN mice bearing AA, achieving the purpose of synergistic treatment of AA. The first combination of minoxidil and tofacitinib in a topical formulation gives a new idea for the clinical treatment of AA.