Fruit and vegetable production across the Mediterranean generates large volumes of by-products that can potentially lessen the livestock feeds deficit in some regions due to climate change effects and other socio-economic factors. However, the utilisation of agro-industrial by-products to their full potential is hindered by several factors such as variability in composition, limited development of preserving technologies and the presence of undesirable substances that may represent a risk for the animal or the final consumer. This work was conducted to study the nutritive value of a range of different alternative by-products from the Spanish agro-industry, assessing the potential to replace conventional ingredients often used in diets for small ruminants and the risk associated with the presence of pesticide residues and minerals. A total of 15 agro-industrial by-products commonly available in different regions of Spain were tested: three different types of apple pomace from three different varieties of apples (Perico, Regona, and Solarina), lemon pulp, avocado seed, broccoli, watermelon silage, olive cake, avocado cake, and six types of silages made with straw and a combination of different by-products (80/20 on fresh matter basis) from the intensive greenhouse horticulture: cucumber, tomato, pepper-cucumber mix (Pep-Cuc silage), aubergine-tomato mix (Aub-Tom silage), tomato-pepper-watermelon mix (Tom-Pep-Wat silage), and watermelon-melon-tomato mix (Wat-Mel-Tom silage). The study involved chemical characterization, including minerals and pesticides residues, and in vitro assessment of the ability to partially replace (10%, 20%, 30%, 50% and 100%) conventional ingredients in a diet for adult sheep (oat hay, barley and sunflower meal), depending on their chemical composition. The inclusion of by-products up to 30% replacement had not effect or improved some of the fermentation parameters and cucumber silage and apple pomace could successfully replace 100% of oat hay and barley, respectively, with only a significant reduction (P < 0.006) of rumen ammonia concentration. The mineral content was highly variable among the by-products with high values of Al in watermelon silage, Cu in olive cake and avocado by-products and Ni and Cr in olive cake. The pesticide residues assessment included 45 different types of compounds commonly used in crop production and three by-products had levels of pesticides residues above the legal limit: watermelon silage had traces of Chlorpyrifos (0.06 mg/kg DM), lemon pulp had Imazalil (0.09 mg/kg DM), and cucumber silage and Wat-Mel-Tom silages had Thiabendazole (0.04 mg/kg DM). Although all by-products showed potential to replace conventional ingredients from a nutritional perspective, the presence of high levels of some minerals and pesticides residues in some by-products requires regular analyses throughout the year or across batches before feeding them to animals.