ABSTRACT This study investigates the process of students’ metacognitive learning about homeostasis, a fundamental biological principle. The research aimed to determine how the metacognitive awareness learning approach (MCLA) affects student perceptions of homeostasis. The research participants were 146 Israeli 10th-grade students (ages 15–16) who were divided into two groups: The MCLA group (MCLAG) (n = 92) received guidance according to the MCLA. The control group (CG) (n = 54) did not receive such guidance. Results disclose the contribution of the MCLA to a better understanding of homeostasis, a fundamental biological principle. Quantitative findings indicate higher achievements by students in the intervention group. Qualitative findings showed differential conceptual understandings regarding homeostasis characteristics, as follows: the MCLA distinctively promoted the following characteristics of homeostasis: efficiency, dynamics of a homeostatic process, and environments. Other characteristics, such as coordination and lack of randomness, control regulation, feedback mechanisms, and multi-systems, were partially promoted by the MCLA. Regarding the energy characteristics, however, the students faced significant challenges in understanding the energy element in the context of homeostasis, indicating a potential for future research. We can deduce that the MCLA can potentially promote the students’ understanding of homeostasis. These results may guide teachers to convey fundamental principles in biology more effectively.