This study aimed to identify the effectiveness of SNEDDS of Pegagan Leaf Ethanol Extract (PLE) to reduce fasting blood glucose (FBG) levels in zebrafish. Centella asiatica (L.) Urb. or pegagan is among the medicinal plants widely used to treat diabetes in Indonesia. Maceration was employed with 70% ethanol to obtain a viscous extract for the formulation of SNEDDS with Capryol 90, Tween 80, and PEG 400 (1:6:3). Antihyperglycemic testing was conducted on five groups, consisting of normal, positive control, negative control, P I treatment, and P II treatment. On Day 1, all except the normal group was induced with 300 mg alloxan and soaked in 2% glucose solution for 7 days. On day 8, the treatment consisted of 25 mg/2 L metformin for the positive control, 100 mg/2 L SNEDDS for P I, 200 mg/2 L SNEDDS for P II, and no treatment for the negative control. The SNEDDS characterization obtained 100.6 ± 3.12 nm particle size and −7.93 ± 0.66 mV zeta potential, indicating that the SNEDDS had fulfilled the requirements of good preparation. The antidiabetic activity test found a 69.90% decline in FBG levels in 100 mg/2 L SNEDDS and 72.20% in 200 mg/2 L SNEDDS.