(1) Background: Considering the autoimmune nature with genetic predisposition of alopecia areata, and the immunomodulatory properties of some probiotics, the present study was conducted in patients with alopecia areata. (2) Method: A 24-weeks randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of an oral probiotic intake in severity of alopecia areata and the effect on skin and gut microbiota. 3) Results: The number of alopecia areata plaques decresed in 56% of patients in the probiotic group vs. 30% in the placebo group. Patients with improvement on the affected skin surface area, showed a results of 45% and 20% in probiotic and placebo groups, respectively. For "activity", "inactivity” and "regrowth", an improvement in 55%, 67% and 55% of patients was respectively observed in the probiotic group, compared to 50%, 40% and 30% in the placebo group. No changes were observed in the gut microbiota during the intervention period. Regarding skin microbiota, changes were detected in the probiotic group, with reductions in characteristic genera during the study. (4) Conclusions: To our knowledge, this is the first clinical trial assessing the efficacy of a probiotic in patients with alopecia areata. This probiotic mixture improves the course and modify the skin microbiota of these patients.