Background: Valproic acid (VPA), is often used as an anticonvulsant drug that activates the Wnt/β-catenin signaling pathway and blocks GSK3b, a glycogen synthase kinase, and though connected with increasing hair growth and induction of anagen. Currently, only FDA-approved two percent topical minoxidil is available therapy to treat female pattern baldness. Objective: This randomized controlled clinical trial study aimed to evaluate the effectiveness of topical VPA and 5% topical minoxidil for treating Female pattern hair loss (FPHL). Patients and methods: This study included 81 patients with FPHL who were allocated into three groups randomly (27 treated with topical sodium valproate-loaded nano spanlastics formulation, 27 treated with minoxidil® 5% lotion, and 27 treated with saline bottled containers using transdermal delivery using a derma roller for 6 months. The included patients were chosen randomly from the Outpatient Clinic of Dermatology, Andrology & STDs Department, Mansoura University Hospitals. All patients were subjected to history taking, and general dermatological and scalp examination. Results: In comparison to the control group, the mean change in the total number of hairs was substantially larger in the VPA and minoxidil groups (P = 0.047). Although the majority of adverse events in both groups were moderate and self-limiting, the variations in prevalence rates across the groups were comparable (P = 0.72). Conclusion: Topical VPA and 5% minoxidil increased the total hair count of our patients ; therefore, topical VPA is a potential therapy option for FPHL.