Abstract During cheese-making, Lactococcus lactis is confronted with various stresses that affect its metabolic activities and, therefore, texture and flavour formation. Our objective was to investigate the behaviour in a cheese model of two L. lactis strains with a common metabolic core but also specific features. Global cytoplasmic proteomes and targeted enzyme activities were analyzed in cells harvested from cheese after 1 and 7 days and metabolite production was determined. In both strains, the adaptation mechanisms to the cheese environment were mainly responses to medium acidification and amino acid starvation. They were induced before day 1 and the pathways thus triggered remained active during ripening. Response intensity differed in the two strains, leading to notable differences in proteome and metabolite production. In particular, we highlighted the importance and consequences of the intensity of initial proteolysis on the global metabolism of L. lactis in cheese.