As an agricultural country, Indonesia has considerable agricultural potential towards development of the national economy. However, the potential itself must be followed by the improvement quality of the agriculture. Armyworm (Spodoptera sp.) is one of the pests that damages various kinds of plants and leads to harm the agricultural sector. One of the ways to control armyworm pests is to provide organic pesticides (bio-insecticides) which are biodegradable and safe for human health. The papain enzyme is one the enzymes obtained from the gum of papaya which functions as a bio-insecticides. The gum of papaya itself comes from waste papaya skin which its availability is abundant in Indonesia. The method that can be used to get the papain enzyme from papaya's gum is the extraction through the help of ultrasonic waves. Natural Deep Eutectic Solvents (NaDES) was chosen as a solvent because its environmentally friendly, to extract the enzyme papain which later will be made into a bio-insecticides. The sonication time of 10, 20, and 30 minutes and the mass ratio of gum per volume of solvents 20, 40, and 60 mg/mL were varied to obtain the optimum conditions in the extraction process which were seen from the results of protein concentration test, enzymatic activity test, and efficacy test. The result of the study showed that 20 minutes and a concentration of 20 mg/mL were the optimum conditions for the extraction process of the papain enzyme. In addition, the use of NaDES solvents compares to ethanol solvents as commonly used solvents, showed that the extraction results with NaDES solvents were better than the results of ethanol solvents.