PurposeThe purpose of this study is to analyze the impact of human capital related to gender and nationality diversity in boards of directors on the innovation of university spin-offs (USOs) in their entrepreneurial ecosystem. Following the intellectual capital (IC) framework and the resource dependence theory, upper echelons theory and critical mass theory, it hypothesizes that the relationship between board diversity and USOs’ firm innovation is non-linear.Design/methodology/approachTo test the research hypotheses empirically, a sample of 827 Italian USOs over the period 2009–2018 was analyzed using zero-inflated Poisson regression modeling. A robustness test was also performed.FindingsGender obstacles remain in USOs’ entrepreneurial ecosystem, with little involvement of women in boards, and the benefits of human capital for firm innovation emerge with increased female representation. Nevertheless, a few foreign-born directors embody valued IC in terms of human capital from an internationally linked entrepreneurial ecosystem, which decreases with more foreign-born directors due to communication costs and coordination problems.Research limitations/implicationsThe emerging non-linear relationships imply that gender- and nationality-diverse boards in USOs constitute critical human capital factors boosting the devolvement of entrepreneurial processes, in terms of firm innovation, in university entrepreneurial ecosystems.Originality/valueThis study contributes significantly to the move from traditional corporate governance analysis through an IC framework, fostering an understanding of the role of human capital and its diversity determinants in spurring firm innovation among USOs considering the university entrepreneurial ecosystem.