The exploitation of agri-food industrial by-products to produce novel foods is a promising strategy in the framework of policies promoting the bioeconomy and circular economy. Within this context, this study aims to examine the effect of food neophobia and food technology neophobia in the acceptance of a novel food by consumers (through an EU research project: Sybawhey). As a case study, a functional yogurt-like product was developed by synergistic processing of halloumi cheese whey, enriched with banana by-products. The present study contributes to the literature by examining consumers’ perceptions for such a novel food, identifying the profile of potential final users and classifying them according to their “neophobic tendency”. A comparative approach among groups from Greece, Cyprus and Uganda was adopted to explore whether respondents have a different attitude towards this novel yogurt. Results suggest that there is a potential for increasing consumption of novel foods derived by agri-food industrial by-products, but more information about the importance of using by-products are required to enhance consumers’ acceptance of this novel food. Such results may be useful to policy makers, aiming to promote strategies towards the effective reuse of food outputs leading to the manufacture of sustainable novel foods.