The prefecture of Kilkis has a large variety of habitats and high diversity of species with many endemic species of flora and fauna. A large number of rare species of flora and fauna are observed in the mountains Dyssoro, Kroussia, Mavrouvouni and Paikos, as well as the vicinity region of Lake Doirani, and the Gallikos and Axios rivers.

The rare ecosystem of the water bodies of Pikrolimni with its mud baths, famous since Homeric years for its healing properties, is included in the network of Natura 2000 sites.