This article presents findings from a qualitative study exploring factors influencing life sciences teachers’ integration of indigenous knowledge (IK) across various topics in grades 10-12, as mandated by the curriculum and assessment policy statement in South Africa. Despite this mandate aiming to enhance accessibility and comprehension, many teachers struggle to integrate IK meaningfully. Through in-depth interviews and lesson observations with five teachers in Gauteng Province, the study reveals challenges such as inadequate training, limited support structures, and negative attitudes towards IK. Observations highlight deficiencies in pedagogical content knowledge related to IK integration. The study suggests intensified teacher training and future research focusing on textbook content and leveraging information and communication technologies to digitize IK and make its integration more meaningful and interesting. This will enhance educational experiences for both the teachers and learners in life sciences classrooms.