In response to the emphasis on DNA in the high school biology curriculum, this study employed Understanding by Design (UbD) theory to design a DNA curriculum that combined backward design, WHERETO elements, and Six Facets of Understanding to improve learning outcomes. The curriculum was implemented in four classes (105 students). One class was given the UbD courses as the experiment group and the other three classes were given the standard courses as the control group. The study investigated the difference in learning outcomes of the two groups of students. This study used both quantitative and qualitative data for analysis. The t-test was used to analyze the quantitative data which were the students’ performance on the DNA structure concept test. The qualitative data included worksheets, short essay summary, DNA model building assignment, and students’ curriculum questionnaire. The findings showed that UbD theory could be used to develop assessments and lesson plans suitable for courses. The students’ performance in UbD courses was significantly higher than the students’ performance in standard courses. Thus, curriculum design based on UbD theory could improve learning outcomes of students’ understanding of the DNA unit.