Abstract The purpose of this research was to propose theoretical elements for the description of the students’ attitudes in the teaching of differential calculus and its applications to physics from the onto-semiotic approach in the affective and interactional suitability. The design of this research with a complementary approach of qualitative and quantitative methods, with predominance of the first one, under the interpretative paradigm. The field modality and a quasi-experimental design to evaluate the applicability of the concepts of differential calculus. The collection techniques were: first, the semi-structured interview, in order to guarantee the depth and density of the information so that it converges in an emerging system of meanings and categories; second, the application of a questionnaire to evaluate the cognitive capacity of students under the onto-semiotic and traditional approach; third, observation through surveys. The findings lead to an instructional process through which mathematical concepts are taught efficiently, the student’s role is valued as being assertive, autonomous, and responsible, while the teacher contributes to the development of emotional support by increasing the student’s motivation, self-confidence, and interest in learning mathematics.