The Indonesian National Assessment set by the government is in line with the Program for International Student Assessment (PISA) assessment which includes students’ scientific literacy skills for a 21st century education succeeds. This study determined the increase in students’ scientific literacy skills through ethnoscience, science, technology, engineering, mathematics or ethno-STEM learning assisted by RE-STEM App. A quasi-experimental design with the type of one-group pretest-posttest design was used to obtain data from the treatment. There were 102 students involved by purposive sampling technique from a 338 population of grade 8 students in a rural secondary school in Central Java, Indonesia. RE-STEM App involves four themes of Indonesian cultures as learning resources, namely tarutu, tin-telephone, calung, and bird whistle. This study revealed that students’ scientific literacy skills increased by 61.33% in the medium category in general, also in each aspect. Research data indicate that the RE-STEM App has supported teachers to improve students’ scientific literacy skills. By applying ethno-STEM through RE-STEM App, teachers can help students to investigate the science concepts in ethnoscience. This strategy proved that ethnoscience aspect can be an important factor in developing students’ scientific literacy skills.