Research has revealed that learning, especially in the field of science, is strongly affected by various factors. These factors include students' attitudes towards the subject matter, and the manner in which the subject is taught. Given their close linkage to students' achievement, attitudes are relevant component in science learning. However, researchers have noticed a decline in students' attitudes in pursuing science. Thus, the aim of this research was to delve into the impact of virtual laboratories on students' attitudes toward biology and their performance in biology topics perceived as difficult. The research involved 168 Rwandan upper secondary school students. The study used a survey research combined with a quasi-experimental research design. The control group comprised 83 students and was taught with the conventional teaching method, while the experimental group comprised 85 and was treated under technology-based instruction using virtual laboratories. Furthermore, a focus group interview was used to get qualitative data about attitudinal change before and after the intervention. Concepts of nerve cells and identification of food nutrients, and enzyme activities were the focus of this study. The results indicated an important effect of an intervention to improve students' attitudes toward the learned topics (p value < 0.05) and performance in favor of the experimental group. The focus group interviews revealed that prion to teaching interventions nerve cells topic was abstract and daunting to students and the visualization exercises helped them to understand while increasing their interest and engagement. However, a significant effect of the treatment on gender was not identified. The study recommends the use virtual laboratories for teaching difficult and abstract concepts to encourage positive attitudes toward learning biology.