The study compared low-dose isotretinoin (≤ 0.5 mg/kg/day) with conventional doses (0.5–1.0 mg/kg/day) in the treatment of acne. They analyzed four randomized controlled trials with 202 patients, with the primary outcome being change in GAGS score at 24 weeks. At 24 weeks, there was no significant difference in efficacy [MD = -1.87, 95% CI (-4.38, 0.64); p = 0.15; I² = 85.67%], heterogeneity decreased after excluding one study to I² = 44.97% with no difference [MD = -0.92, 95% CI (-2.62, 0.77); p = 0.28]. Post-treatment deterioration did not differ [MD = 0.10, 95% CI (-1.67, 1.86); p = 0.91; I² = 0%]. Low doses had higher patient satisfaction [SMD = 0.99, 95% CI (0.63, 1.34); p < 0.001] and better tolerability. The certainty of the evidence is low for efficacy and moderate for safety and satisfaction (GRADE). The studies focused mainly on moderate acne without concomitant interventions.