Bacteria face diverse environmental challenges, such as changes in temperature, pH, and osmolarity, and exposure to antibiotics, which necessitate adaptive responses for survival. The chromosome-structuring nucleoid-associated proteins (NAPs) are key to these responses owing to their role in global gene regulation. In this review, we summarize the functional interplay between environmental challenges and NAPs, and the adaptive responses mediated by NAPs. Specifically, physicochemical environmental factors modify the transcription level of NAP genes and affect protein activity, which facilitates bacterial adaptation via a short-term strategy. Additionally, NAPs regulate horizontally transferred genes, such as those involved in antibiotic resistance and virulence, by affecting their expression and integration into the host genome. Via this long-term strategy, NAPs contribute to both stress resilience and the evolution of bacterial traits, ensuring survival under environmental stress while facilitating genetic diversity through horizontal gene transfer.