The study aimed at investigating the effectiveness of teaching Biology at primary school by playing and using a laboratory approach, in a limited-resources learning environment with additional restrictive rules due to the current pandemic emergency. It also investigated the possibility of dealing with Microbiology topics, such as microorganisms and their role in human life. These topics are traditionally not taught at primary school, particularly at third grade. The research process was based on the hypothesis that the adopted methodology may be useful to foster the active co-construction of knowledge and to increase the pleasure in learning. It makes pupils the main subjects of their learning process, with positive impacts on interest towards Science and on building an active citizenship. First of all, an online survey about Science, Microbiology and Health Education teaching was supplied. The sample consisted of teachers and parents of the school in which the research was carried out and of the Venice province. Then, a test about foreknowledge and interest towards Science and microorganisms was submitted to students. Outcomes were analysed in order to identify the experimental and the control group among two primary school third grade classes in a town of the Venice province. The experimental group was tested with activities characterized by the application of the scientific method and the learner-centred approach, engaging from an emotional, sensory and playful point of view. The control group was, instead, tested with a traditional and teacher-centred approach. Tests and ongoing observation data supported the possibility of teaching Microbiology topics using both the approaches. The laboratory approach was more successful than the traditional one in knowledge acquisition but that is a subtle difference. The effectiveness was more significant in: developing interest towards Science and microorganisms, implementing inclusion and enhancing participation, promoting pleasure in learning and limiting negative feelings linked to the topics.