Diabetes mellitus is a heterogeneous metabolic disorder characterized by an increase in blood sugar levels due to insulin disorders. Current treatment for diabetes mellitus focuses on controlling and lowering blood glucose. However, long-term treatment for diabetes mellitus can have side effects that cause several medical problems. Medical therapy using natural ingredients as an alternative therapy is currently being considered because of its potential and minimal side effects. Patikan kebo is a natural ingredient containing the flavonoid quercetin group. However, the antihyperglycemic effect of the patikan kebo leaves is not known with certainty. This study aimed to determine the effect of patikan kebo leaf extract (EDPK) on the levels of GDP, insulin, HOMA-IR, and HOMA-β in male rats with diabetes mellitus induced by streptozotocin (STZ) and nicotinamide (NA). The design of this study was a pre-and post-test control group design. 42 male Wistar rats were divided into 7 groups: K (normal mice), KN (DMT2 mice without intervention), KP (DMT2 mice intervened with acarbose 1.8 mg/kg BW/day), P1 (DMT2 mice intervened with EDPK dose 75 mg/kg BW/day), P2 (DMT2 mice intervened with EDPK dose 150 mg/kg BW/day), and P3 (DMT2 rats intervened with EDPK dose 300 mg/kg BW/day). The intervention was given for 7 and 15 days. The data were statistically analyzed using the Two Way ANOVA test. EDPK was proven to decrease GDP and HOMA-IR levels and increase insulin and HOMA-β in the male Wistar rat model of diabetes mellitus induced by STZ+NA. EDPK with a dose of 300 mg/kg BW/day proved to have the strongest antihyperglycemic effect.