Flipped learning is a pedagogical approach that has evolved from the variations of blended learning and involves prior study which emphasizes self-directed learning. This study aims to design instructional materials to harness learning skills, strengthen the mastery of cognitive skills, and help learners thrive and succeed in the 21 st century. The flipped learning concept has been analyzed to design and develop learning widgets and instructional design models to learn Biology. The design of instructional materials was anchored on the framework for 21 st century learning that identifies the skills and knowledge that the students need to succeed in work and life in the 21 st century. The different learning tasks in the created instructional materials were appropriately designed to capture the 4 Cs - critical thinking, collaboration, communication, and creativity of the students and were tailored fit for a flipped approach to learning Biology.