Objective To explore the effect of nanocrystal microneedle introduction of 5% minoxidil combined with compound glycyrrhizin on terminal hair density in patients with mild alopecia areata. Methods A total of 60 patients with mild alopecia areata admitted to our hospital from January 2024 to December 2024 were selected and divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group was treated with nanocrystal microneedle introduction of 5% minoxidil, and the observation group was treated with nanocrystal microneedle introduction of 5% minoxidil combined with compound glycyrrhizin. The terminal hair density, treatment effect, hair follicle-related molecular indexes and adverse reaction rate were compared between the two groups. Results The terminal hair density in the observation group was better than that in the control group at 8 and 12 weeks after treatment (P <0.05). The total effective rate in the observation group (93.33%) was higher than that in the control group (73.33%) (P <0.05). The inhibition rates of Fas and FasL expression in hair follicles in the observation group after treatment were higher than those in the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion The treatment of mild alopecia areata with nanocrystal microneedle introduction of 5% minoxidil combined with compound glycyrrhizin has a good effect, which can optimize the terminal hair density, improve the expression of hair follicle-related molecular indexes, and does not increase the risk of adverse reactions, with definite clinical application value.