Abstract: This study focuses on the innovation practices of specialized, refined, distinctive, and innovative “little giant” enterprises in the era of big science. Based on the theory of knowledge recombination, it delves into the impact of disciplinary diversity in scientific collaboration on radical technological innovation in these enterprises. Through empirical analysis of unbalanced panel data from 2,464 “little giant” enterprises in the new materials field spanning from 2000 to 2018, the study finds that disciplinary diversity in scientific collaboration has a positive effect on radical technological innovation in “little giant” enterprises, with knowledge complementarity partially mediates this relationship. Additionally, the intensity of intellectual property protection negatively moderates the relationship between disciplinary diversity and knowledge complementarity, while technological turbulence positively moderates the relationship between knowledge complementarity and radical technological innovation in enterprises. This study not only elucidates the mechanism through which disciplinary diversity in scientific collaboration influences technological innovation in “little giant” enterprises but also reveals the boundary conditions of this mechanism. The conclusions of this paper contribute to a deeper understanding of the facilitating role of interdisciplinary scientific collaboration in technological innovation among small and medium-sized enterprises.