One of the most significant global public health issues is malaria. Combination treatment of S. ligustrina blum wood with Dihydroartemisinin-piperaquin phosphate (DHP) as an antimalaria to increase the effectiveness of S. ligustrina blum wood extract. The purpose of this study was to see how effective the combination of aquadest extract (AE) and 25% ethanol extract (EE) of S. ligustrina blum wood with DHP was against P. berghei ANKA. S. ligustrina blum wood extract were extracted by maceration using aquadest and 25% ethanol. The extract formulated into capsules with or without DHP. Fifty DDY mice were divided into 10 groups (n = 5). Group I was infected infected-untreated, group II was received 25 mg/kg BW of dihydroartemisinin and 197 mg/kg BW of piperaquine phospate, and the others group of mice inoculated with 1x106
P. berghei ANKA and treated with 200 mg/kg. Blood samples were taken every day, starting from the first day to the tenth day. The number of parasites and erythrocytes was calculated using the image photoshop program, then the percentage of parasitemia and inhibition was determined. There was no difference between AE and EE in combination with half dose of DHP with DHP control, but significantly different with infection control. S. ligustrina blum wood extract worked synergistic with DHP as an antimalaria with a percentage of inhibition approaching 100% on the 10th day after treatment. S. ligustrina blum wood extract has the potential to be developed as an effective and safe combination antimalaria drug with pure chemical active ingredients.