Sicily is a Mediterranean island with an exceptional natural heritage, where gypsum outcrops are widespread and associated with an endemic flora. These ecosystems are prioritized by the European Habitats Directive (Mediterranean gypsum steppes, 1520*) in the Mediterranean Basin. Some studies have revealed the physiological mechanisms in gypsophile plants, which are important adaptative characteristics of plants that live on gypsum. To identify stress-tolerant strategies, we studied the leaf chemical composition of 14 plant species (gypsum endemics, Mediterranean gypsophiles and widely distributed) from Sicily. The ability to accumulate mineral elements in leaves, especially sulfur (S), calcium (Ca) and magnesium (Mg), is a widespread strategy for gypsophile plants. Bioconcentration factor (BCF) calculations also indicate bioaccumulation of carbon (C), nitrogen (N), and potassium (K) in species with a certain degree of foliar succulence, such as Gypsophila arrostii Guss. subsp. arrostii or Diplotaxis harra (Forssk.) Boiss. subsp. crassifolia (Raf.) Maire, which also accumulates Mg and Sodium (Na). The narrow gypsophile Erysimum metlesicsii Polatschek exhibited the highest BCF value for strontium (Sr). The study of the gypsophile G. arrostii subsp. arrostii growing on limestone substrates indicates that this plant tends to hyperaccumulate nutrients, such as S, that are normally available in gypsum substrates. The remarkable ability of these plants to absorb elements such as sulfur and strontium is important to explain their ecological adaptations but also indicates their potential usefulness in environmental phytoremediation processes. The study of plant communities and flora of gypsum substrates is essential to understand the nutritional adaptations that allow flora to survive in gypsum environments and to support the better preservation of these interesting natural areas in Sicily.