In this study, 210 articles were reviewed from two databases—Web of Science and Scopus—using the systematic literature review method, following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) selection and analysis process. Through systematic literature review and statistical analysis of empirical research articles, this study takes the community of inquiry (CoI) framework as theoretical support, tries to clarify blended learning instructional design methods based on the CoI framework based on understanding the thematic distribution of the existing literature, and provides a deeper understanding of the application of the CoI framework in the blended classroom. Hence, blended instructional design can be approached from the perspective of both teachers and learners. Students' personalized learning, collaborative learning, peer interaction, and student engagement are targeted to be strengthened. Teachers, on the other hand, should consider teacher-student interactions, teacher roles, instructional materials and environments, and mobile learning.