The Mediterranean diet features plant-based foods renowned for their health benefits derived from bioactive compounds. This review aims to provide an overview of the bioactive molecules present in some representative Mediterranean diet plants, examining their human nutrigenomic effects and health benefits as well as the environmental advantages and sustainability derived from their cultivation. Additionally, it explores the facilitation of producing fortified foods aided by soil and plant microbiota properties. Well-studied examples, such as extra virgin olive oil and citrus fruits, have demonstrated significant health advantages, including anti-cancer, anti-inflammatory, and neuroprotective effects. Other less renowned plants are presented in the scientific literature with their beneficial traits on human health highlighted. Prickly pear’s indicaxanthin exhibits antioxidant properties and potential anticancer traits, while capers kaempferol and quercetin support cardiovascular health and prevent cancer. Oregano and thyme, containing terpenoids like carvacrol and γ-terpinene, exhibit antimicrobial effects. Besides their nutrigenomic effects, these plants thrive in arid environments, offering benefits associated with their cultivation. Their microbiota, particularly Plant Growth Promoting (PGP) microorganisms, enhance plant growth and stress tolerance, offering biotechnological opportunities for sustainable agriculture. In conclusion, leveraging plant microbiota could revolutionize agricultural practices and increase sustainability as climate change threatens biodiversity. These edible plant species may have crucial importance, not only as healthy products but also for increasing the sustainability of agricultural systems.