Purpose <p>Pregnant women are at heightened risk for severe COVID-19 outcomes. However, treatment options during pregnancy remain limited due to concerns over their safety and efficacy.</p> Methods <p>This systematic review and meta-analysis assessed the safety and efficacy of nirmatrelvir-ritonavir in pregnant women diagnosed with mild-to-moderate COVID-19. The analysis focused on cases where the treatment was initiated within five days of symptom onset. A single-arm meta-analysis was performed to comprehensively evaluate outcomes across maternal, delivery, and neonatal domains.</p> Results <p>In line with PRISMA guidelines, six studies involving a total of 427 pregnant patients were included in the analysis. Hospitalization was reported in 2% of patients (95% CI: 1%–5%), with low heterogeneity across studies (I² = 21.9%). Drug discontinuation and new-onset gestational diabetes (NOGDM) had a pooled estimate of 0.7% (95% CI: 3% to 15%) and 4.0% (95% CI: 1% to 16%), respectively, with substantial heterogeneity (I² = 64.7% and 66.5%), respectively. New-onset gestational hypertension (NOGHTN) had a pooled estimate of 4% (95% CI: 1% to 26%), with considerable heterogeneity (I² = 78.81%). For neonatal outcomes, the pooled estimate for birth weight was 3186 g (95% CI: 3123–3248 g; I² = 0%), and no maternal or neonatal deaths were reported across the included studies.</p> Conclusion <p>Nirmatrelvir-ritonavir appears safe and effective for mild-to-moderate COVID-19 in pregnant women, with low rates of hospitalization and adverse maternal outcomes. Larger, randomized studies are crucial to confirm these findings and ensure safety in diverse populations.</p>