Background: There is scarce information on the efficacy of alternative medicine (AM) alone as a treatment for newly diagnosed acute leukemia in children. We aimed to compare overall survival (OS) between children with newly diagnosed acute leukemia who received AM alone as the first-line treatment and those treated with conventional chemotherapy (CCT). Methods: Two-to-one nearest-neighbor propensity score-matching using sex, initial white blood cell count, phenotype of leukemia, and period of diagnosis was performed on 184 patients who received CCT and 92 who received AM alone after being diagnosed with leukemia. A multivariable Cox proportional-hazards regression model was then applied to assess the effect of treatment on OS after adjusting for potential confounders. Hazard ratios (HR) and 95% confidence intervals (CI) are provided. Results: After adjusting for initial white cell count and subtype of leukemia, children treated with AM alone had worse OS (HR 5.14, 95% CI 3.75–7.04) than those given CCT. The 5-year OS rate for newly diagnosed acute leukemia treated with AM medicine alone was 0%. Conclusion: AM without CCT is associated with poorer survival when compared with CCT.