Introduction Streptococcus thermophilus is a Gram-positive bacterium widely used as starter in the dairy industry as well as in many traditional fermented products. In addition to its technological importance, it has also gained interest in recent years as beneficial bacterium due to human health-promoting functionalities. The objective of this study was to inventory the main health-promoting properties of S. thermophilus and to study their intra-species diversity at the genomic and genetic level within a collection of 79 representative strains.2. Methods FastANI software was used to compute pair-wise ANI (Average Nucleotide Identity) values to confirm that the 79 selected genomes belong to the same species. MicroScope Pan-genome analysis tool and eggnog-mapper were used to analyse core and accessory genome. Text mining was used to highlight pseudogene annotations. AntiSMASH and BAGEL4 were used to search bacteriocins sequences and ABRicate to search antibiotic resistance genes. R and Python libraries were used to create heatmaps. 3. Results In this study various health-related functions were analyzed at the genome level from 79 genome sequences of strains isolated over a long time period from diverse products and different geographic locations. While some functions are widely conserved among isolates (e.g., degradation of lactose, folate production) suggesting their central physiological and ecological role for the species, others including the tagatose-6-phosphate pathway involved in the catabolism of galactose, and the production of bioactive peptides and gamma-aminobutyric acid are strain-specific. Most of these strain-specific health-promoting properties seems to have been acquired via horizontal gene transfer events. The genetic basis for the phenotypic diversity between strains for some health-related traits have also been investigated. For instance, substitutions in the galK promoter region correlate with the ability of some strains to catabolize galactose via the Leloir pathway. Finally, the low occurrence in S. thermophilus genomes of genes coding for biogenic amine production and antibiotic resistance is also a contributing factor to its safety status. 4. Conclusions The natural intra-species diversity of S. thermophilus, therefore, represents an interesting source for innovation in the field of fermented products enriched for healthy components. A better knowledge of the health-promoting properties and their genomic and genetic diversity within the species may facilitate the selection and application of strains for specific biotechnological and human health-promoting purpose. Moreover, by pointing out that a substantial part of its functional potential still defies us, our work opens the way to uncover additional health-related functions through the intra-species diversity exploration of S.thermophilus by comparative genomics approaches.