Climate change affects the sustainability of farming systems by downgrading soil fertility and diminishing crop yields. Agenda 2030 for Sustainable Development Goals aims to achieve key performance indicators to convert effectually currently degraded agroecosystems into smart, climate-resilient, and profitable farming systems. The introduction of alternative crops could equilibrate the negative impact of increased temperatures and water scarcity to ensure sufficient farm profitability. Alternative crops such as quinoa, teff, tritordeum, camelina, nigella, chia, and sweet potato show a high acclimatization potential to various conditions and could be components of novel re-designed agroecosystems, satisfying the goals the EU Green Deal for reduced chemical input use by 2030. In certain occasions, they adapt even better than conventional or traditional crops and could be integrated in crop rotations, demonstrating multiple uses that would benefit farmers. This review aimed to (i) evaluate seven alternative crops based on their potential contribution to climate change mitigation, in compliance with the EU (European Union) Green Deal objectives and the SDGs (Sustainable Development Goals) of the UN (United Nations), and (ii) examine the factors that would determine their successful integration in the Mediterranean Basin. These limiting factors for crop establishment included (i) soil properties (soil texture, pH value, salinity, and sodicity), (ii) environmental parameters (temperature, altitude, latitude, photoperiod), and (iii) crop performance and dynamics regarding water demands, fertilization needs, light, and heat requirements. All proposed crops were found to be adaptable to the Mediterranean climate characteristics and promising for the implementation of the goals of EU and UN.