There has been incessant low academic performance in Mathematics especially among female in colleges of education for some time. Thus, this study sought to find the sex differences and academic performance in Mathematics-based students’ disciplines in Colleges of Education in Ilesa and Ila Orangun, both in Osun State, Nigeria. The research adopted pre-test post-test control group quasi experimental design. The study comprised of six mathematics combinations at the 300 level of Schools of Science and Arts & Social sciences in the two government owned Colleges of Education, Osun State. 130 students were sampled for the study. The two instruments used for data collection were Mathematics Performance Test and Mathematics Attitudinal Scale. The hypotheses generated were tested using t-test analysis. The study revealed that there was no visible difference between the attitude of male and female students while there was a significant difference in the performance of male and female students when exposed to instructional aids. The outcome of the study is expected to influence policy, decision making and other stakeholders on female students’ better performance in the subject. It is recommended that lecturers should intensify efforts to encourage female students not minding the sex and give them equal opportunities in the class room in order to build their confidence in the subject. Keywords: Academic, Differences, Mathematics-Based, Performance, Sex, Students,