This study explored what challenges teachers experienced when integrating indigenous knowledge systems (IKS), which are culture specific, into practical work in natural sciences classrooms with diverse learners. Using an exploratory qualitative case study based on an interpretive paradigm, three natural sciences teachers and two subject advisors were purposively selected from the Harry Gwala district in the KwaZulu--Natal province of South Africa. Semi-structured interviews, a focus group interview and practical work lesson observations were used to collect data that were analysed using thematic content analysis. The findings show that when indigenous knowledge was integrated with practical work, real-life activities were simulated in the classrooms. The introduction of real-life situations and IKS-based practical activities invited IKS-based learner behaviour. When simulating real-life practices, the learners' socio-cultural beliefs became manifest. It was reported that learners assigned traditional gender roles for the practical work activities. Recent initiates into adulthood did not participate in activities that included the use of open fires because it was forbidden in their culture. Learners were also not willing to work with clay soil based on the belief that it attracted goblins, despite evidence showing its use in the building of huts and making of pots. Furthermore, teachers recognised the need to manage the conflicts and controversies that might result from integrating IKS into practical work. The study recommends education districts to establish contextualised resource centres for IKS integration that take into account the socio-cultural beliefs of local learners as a way to support the teachers.