The domestication of wild-growing plants, including cultivation and fertilization protocols, is able to alleviate the ecological risks posed by the uncontrolled harvesting of range-restricted local endemic plants. In this field study focused on Verbascum arcturus, a vulnerable local endemic of Crete (Greece), the effect of two kinds of fertilization applied by two methods (foliar/root) was investigated. The foliar application included conventional or integrated nutrient management (INM) fertilization. Root application included the application of conventional fertilizers, biostimulants, or INM with biostimulants. Several properties of plant growth, physiology and nutrition were determined. The results showed that fertilization treatment affected neither leaf color and shape nor plant growth, morphology, dry mass partitioning or nutrient content. However, both kinds of foliar-applied fertilization enhanced Zn and B in leaves and soil-applied biostimulant increased leaf Ca. Considering both chlorophyll and antioxidant compounds’ content, foliar application of the INM fertilizers, as well as soil application of the conventional fertilizers or biostimulants, could be considered as accepted options. This study reports for the first time an assessment of the total phenolic and flavonoids content evidenced in V. arcturus and encourages the use of fertilization in promoting the herbal antioxidant profile without compromising visual quality or yield. The findings of this study could be considered as a documented contribution toward the sustainable exploitation of V. arcturus.