Androgenetic alopecia (AGA) is a common type of hair loss in men and efficacy and safety of current medical treatment remain limited. Therefore, the present study aimed to investigate the efficacy and safety of botulinum toxin type A (BTA) combined with Minoxidil in patients with AGA. 60 male patients were included in this study and control group received topical 5% Minoxidil and the treatment group received BTA combined with topical 5% Minoxidil. BTA injections (60-70 U) were administered at 30-35 scalp sites. Head photographs were taken at baseline, 2nd, 4th, and 6th months. Clinical descriptions recorded scalp conditions, and patient satisfaction along with Dermatology Life Quality Index scores were documented. The treatment group (TG) showed significant hair growth differences compared to the control group (CG) at the 4th month (P < 0.001) and 6th month (P = 0.0046) post-treatment. TG had improved Investigator Global Assessment (IGA) scores in the 4th month (P = 0.0001) and 6th month (P = 0.0259) compared to CG. Patient satisfaction in TG for hair growth and scalp improvement was higher than CG (all P < 0.05). TG exhibited substantial quality of life improvement at the 4-month (P = 0.0009) and 6-month (P = 0.0099). No adverse reactions were observed post-botulinum toxin injection. BTA combined with Minoxidil effectively promotes hair growth, enhances the quality of life, and alleviates scalp symptoms in male AGA patients at 4th and 6th months, with no adverse effects compared to Minoxidil alone.Trial registration number: Ethics Committee of Shanghai Tongji Hospital (ID: K-2018-026).