The Rgg-like regulators, a family of transcription factors commonly found in many Gram-positive bacteria, play multiple roles, especially in the control of pathogen virulence. Here, we report an rgg homologue from a Chinese isolate, 05ZYH33, of Streptococcus suis serotype 2 (SS2). Deletion of the rgg gene in SS2 increased its adhesion to Hep-2 cells and hemolytic activity in vitro. Significantly, inactivation of the rgg gene attenuated SS2 virulence in an experimental piglet infection model. Using DNA microarrays and quantitative reverse transcription-PCR, we found that the Rgg regulator affects the transcriptional profile of 15.87% (n = 345) of all of the annotated chromosomal genes, including those involved in nonglucose carbohydrate metabolism, DNA recombination, protein biosynthesis, bacterial defense mechanisms, and others. It was experimentally verified that the deletion of rgg in SS2 reduced the utilization of nonglucose carbohydrates, such as lactose and maltose. In addition, the rgg gene was found to be associated with changes in the bacterial microscopic phenotype and growth curve. These data suggested that Rgg in SS2 is a global transcriptional regulator that plays an important role in promoting SS2 bacterial survival during pathogen-host interaction.