Origanum dictamnus L. (Lamiaceae), a local endemic plant of Crete (Greece), creates polysaccharide-containing subcuticular compartments presenting biological activity against phytopathogenic fungi, and, among others, significantly affects the fungal cell wall polysaccharides. This field study introduces a fertilization scheme for O. dictamnus, which was developed and refined to optimize the yield as well as critical herbal quality aspects. Five fertilization schemes were investigated, based on a polysaccharide-based Integrated Nutrient Management (INM), a mixture of conventional inorganic fertilizers (ChF) and two biostimulants (not algae) via foliar and soil application. Plant growth, together with leaf chlorophyll fluorescence and color (SPAD meter, DA meter, Chroma Meter) were determined. The leaf content of chlorophyll, three critical antioxidant compounds (carotenoids, flavonoids, phenols) and nutrients were also assessed. Considering all three antioxidants together, the enhanced efficiency, non-toxic, water-soluble, polysaccharide-based INM by foliar application was the most stimulatory scheme, playing an important role in plant growth and development. The present field study provides, for the first time, baseline fertilization data improving key herbal quality features in O. dictamnus and unravels the attainment of high antioxidant properties. The latter may be exploited in favor of its further utilization as a raw material for tea preparation, medicinal purposes, natural food flavoring and/or food preservative.