New treatment modalities are rising for better clinical improvement in alopecia areata. This work aims to evaluate the efficacy of fractional CO2 laser and microneedling as a transepidermal drug delivery in cases with alopecia areata. The study included 30 patients with alopecia areata. All lesions in each patient have received randomly two different treatment modalities, fractional CO2 laser or microneedling followed by triamcinolone acetonide (TA) application according to group assignment. Sessions were done every month for a maximum of six sessions or complete resolution. Response to treatment was assessed on SALT score and dermoscopic imaging. Both treatment modalities showed a significant clinical improvement of alopecia areata, with a statistically significant reduction of SALT score for fractional CO2 laser group and microneedling group (p value <0.001). Moreover, there is a significant difference in the SALT score between both modalities (p = 0.013), whereas the reduction of the SALT score was more evident in microneedling group. On comparing the dermoscopy findings in fractional CO2 laser and microneedling treated areas before and after treatment, a significant reduction was found regarding all dermoscopic findings of alopecia areata. Fractional CO2 laser and microneedling as a transepidermal drug delivery could be a novel and effective treatment modality in alopecia areata. Dermoscopy is very useful to identify disease activity and early signs of clinical improvement during treatment.