One way of ensuring gender equality in science education is by mainstreaming gender components into the pedagogical delivery of science instruction. Thus, the researchers in this study designed a Gender Responsive Collaborative Learning Strategy (GR-CLS) based on Universal Design for Learning (UDL) principles. The effectiveness of this instructional paradigm on students' achievement and attitude was determined in a mixed factorial quasi-experimental research design study conducted in a virtual and hands-on laboratory learning environment. Multistage sampling technique was used to select a total sample of 218 secondary school students from same sex and mixed sex schools. The six hypotheses formulated in the study were tested using Means and Analysis of Covariance (ANCOVA). Empirical findings revealed a significant difference in the mean achievement and attitude scores of both male and female students who were exposed to GR-CLS under virtual and hands-on laboratory environment respectively compared to those who were not exposed to GR-CLS. These results indicate that GR-CLS is an effective pedagogical strategy for improving students' achievement and attitude regardless of gender. Nevertheless, it was discovered that GR-CLS leads to a significant improvement in the achievement of students from same sex schools over mixed sex schools. The study, therefore, recommends the adoption of GR-CLS by science teachers in the planning and implementation of science lessons to create equal opportunities for both male and female students to benefit maximally from learning activities carried out in the laboratory.