Symptomatic, chemotherapy-related hypoglycemia is a rare complication associated with the administration of purine analogs. The aim of the study was to evaluate 24 h glucose variability and frequency of hypoglycemia among patients with acute lymphoblastic leukemia (ALL) during maintenance therapy (MT). Eighteen children with ALL underwent continuous glucose monitoring (CGM). The number of episodes of hypoglycemia and glucose variability were analyzed. Serum alanine aminotransferase, asparagine aminotransferase, and γ-glutamyl transferase levels were measured as liver function markers. The mean glucose level in CGM equaled 105 ± 13 mg/dL, with standard deviation (SD) 13.8 ± 6.1 mg/dL, and the mean amplitude of glycemic excursions (MAGE) equaled 44.7 ± 19.9 mg/dL. Eight patients had at least one measurement below 70 mg/dL while four patients had measurements below 50 mg/dL. Children with hypoglycemia in CGM examination had a lower median body mass index standard deviation score (BMI Z-score) (-0.65 [-0.94 to -0.27] vs. -0.14 [-0.29 to 0.35]; p = 0.05) and shorter duration of MT (6.5 [4-15] vs. 22.5 [16.5-28] weeks; p = 0.004). Glucose variability parameters were strongly correlated with BMI Z-score and liver function enzymes. Hypoglycemia, particularly at night-time, may develop as a complication of MT in children with ALL. The risk factors for low glucose level are low BMI Z-score and initiation of MT.