Abstract Background Melasma is a common acquired pigmentary disorder that manifests as symmetric hyperpigmented macules and patches on the face, more frequently affecting women of reproductive age. Various underling risk factors have been implicated in the etiology of melasma including; Genetic factors, pregnancy, oral contraceptives, endocrine dysfunction, hormone treatments, cosmetic contact sensitivity and exposure to ultraviolet (UV) light. Management of melasma is a frustrating experience both for the treating doctors and patients because of its recurrent and often recalcitrant nature. Numerous therapeutic modalities have been tried for this condition such as hydroquinone, kligman’s formula (hydroquinone + steroid + tretinoin), kojic acid, azelaic acid, arbutin, ascorbic acid, chemical peels, lasers, tranexamic acid, rucinol, oligopeptides, silymarin, orchid extracts, and various botanical extracts with variable success rates. Objectives Our aim was to assess and compare the therapeutic effects of topical metformin solution 30% with microneedling versus topical tranexamic acid (4mg\ml) solution with microneedling in treating patients with facial melasma. Patients and Methods This is a split-face study included 35 patients with facial melasma. The patients recruited from the Outpatient Dermatology Clinic at Ain Shams University Hospitals. Topical metformin 30% solution with microneedling sessions were done for the right side of the face (4sessions - two weeks apart), and topical tranexamic acid solution (4mg/ml) with microneedling on the left side of the face (4 sessions – two weeks apart). The patients were followed up for 3 months. The response of treatment was evaluated by Hemi MASI score and Antera 3D camera. Results Our study revealed that both microneedling followed by topical metformin solution and microneedling followed by topical TXA solution were efficient in treatment of facial melasma as shown by significant decrease in h-MASI score and average melanin level assessed by Antera camera. Although statistically insignificant, the percentage of change in h- MASI score was more evident with TXA treatment than metformin treatment. The side effects were limited and transient in the form of erythema, burning sensation, and xerosis. The main problem with either treatment was the high relapse rate. Conclusion Both metformin and tranexamic acid applied topically following microneedling sessions led to statistically significant improvement of melasma according to Hemi MASI scores. Topical metformin appears to be a promising therapeutic option in the treatment of melasma without serious adverse effects.