Melasma is a chronic pigmentary disorder characterized by symmetric, hyperpigmented macules and patches on sun-exposed areas, most commonly the face. It disproportionately affects women and is associated with significant psychosocial distress. Among emerging therapies, tranexamic acid (TXA), an antifibrinolytic agent with anti-melanogenic properties, has gained attention as both an oral and topical treatment option. However, comparative data on route-specific efficacy and safety have remained limited. A recent prospective study compared the effectiveness and safety profiles of oral and topical TXA in patients with moderate-to-severe melasma. Participants were randomly assigned to receive either oral TXA tablets or topical TXA formulations over a defined treatment period. Clinical improvement was evaluated using the Melasma Area and Severity Index (MASI), standardized digital imaging, and patient-reported outcomes. Safety was assessed through monitoring of adverse events and laboratory parameters. Results demonstrated that both oral and topical TXA significantly reduced MASI scores from baseline, with improvements visible within the first 8 weeks and sustained throughout the study duration. Patient satisfaction scores were similarly high in both groups, indicating clinically meaningful benefit regardless of administration route. Importantly, the incidence of adverse effects was low across both arms. Mild gastrointestinal discomfort was occasionally reported in the oral TXA group, while transient local irritation was observed in the topical TXA group. No serious adverse events or thromboembolic complications were reported, reinforcing the safety profile of both approaches. The findings suggest that oral and topical TXA offer comparable efficacy in melasma treatment, with similarly favorable safety outcomes. This provides clinicians with flexibility in tailoring treatment to patient preference, tolerability, and convenience. For patients reluctant to take systemic therapy, topical TXA represents a viable alternative, while oral TXA may be preferable for those seeking systemic benefits or with extensive involvement. Overall, this study supports the role of TXA as a versatile therapeutic agent in melasma management. Long-term studies with larger cohorts are warranted to confirm durability of response and further evaluate relapse rates post-treatment.