Background: The combination of diphenylcyclopropenone (DCP) and anthralin may demonstrate synergistic effects in the treatment of chronic extensive alopecia areata (AA). Objective: The objective of the study was to compare the efficacy of the combination therapy of topical DCP and topical 0.5% anthralin versus topical DCP alone for the treatment of chronic extensive AA. Materials and Methods: Ten patients were included in the study. Of these, 1, 2, and 7 patients were diagnosed with alopecia totalis, severe AA (>50% hair loss), and alopecia universalis, respectively. For each patient, one side of the scalp was treated with a DCP solution and 0.5% anthralin for 6 months, while the other side was treated with DCP and a cream base for the same duration. The clinical responses were assessed at baseline and then monthly until the end of the 6-month study period using the Severity of Alopecia Tool score. The side effects were evaluated at each follow-up visit. Results: The difference in the efficacies of the combination treatment and DCP alone was not statistically significant (P = 0.59). Regarding the side effects, DCP plus 0.5% anthralin caused significantly more excessive dermatitis than DCP alone (7 patients vs. 2 patients; P = 0.02). Eight patients reported temporary hyperpigmentation at the combination-treatment site, whereas no hyperpigmentation was reported at the DCP-alone site of any patient (P < 0.001). Conclusions: The combination of DCP and 0.5% anthralin was not superior to DCP alone for the treatment of chronic extensive AA. An increase in side effects – excessive dermatitis and hyperpigmentation – was observed in the combination-treatment group.