Green roofs could be a way to increase vegetation in the center of old Mediterranean cities. The need for conservation of local character and biodiversity requires the use of native plant species, whereas the deficiency of water, particularly in semiarid regions, requires the use of species with reduced irrigation needs. Moreover, the aged buildings lead to the use of lightweight green roof constructions. Therefore, research was undertaken to investigate the possibility of using three Mediterranean aromatic xerophytes, Artemisia absinthium L., Helichrysum italicum Roth., and H. orientale L., at an extensive green roof in Athens, Greece. Simultaneously, the possibility of using locally produced grape marc compost was investigated. Substrate type and depth and irrigation frequency effects on growth of these species were studied. Rooted cuttings were planted mid-May in plastic containers with a green roof infrastructure fitted (moisture retention and protection of the insulation mat, drainage layer, and filter sheet) and placed on a fully exposed third floor flat roof at the Agricultural University of Athens. Two types of substrates were used, grape marc compost:soil:perlite (2:3:5, v/v) and peat:soil:perlite (2:3:5, v/v, as a control), as well as two substrate depths, 7.5 (shallow) and 15 cm (deep), and two irrigation frequencies, sparse (5 or 7 days in shallow and deep substrate, respectively) and normal (3 or 5 days in shallow and deep substrate, respectively). Increased contents of macroelements, total phosphorus (P) and potassium (K) in particular, were recorded in the compost-amended substrate, whereas both substrates had similar physical properties. Plant growth was recorded from May to October. The deep compost-amended substrate, independent of irrigation frequency, resulted in taller plants with bigger diameter and aboveground dry weight in all species. However, a remarkable result was that shallow compost-amended substrate with sparse irrigation resulted in similar or even bigger plant growth of all plant species compared with deep peat-amended substrate with normal irrigation. Thus, all three species were found suitable for use in Mediterranean extensive or semi-intensive green roofs, whereas the use of grape marc compost in the substrate allowed for less water consumption and the reduction of substrate depth without restriction of plant growth at the establishment phase and the first period of drought.