Streptococcus suis is a zoonotic pathogen causing substantial economic losses to the pig industry, as well as being a human health burden due to infections worldwide, especially in Southeast Asia. In Thailand, there was high cumulative incidence in humans during 1987–2021, mostly in males. At least five large outbreaks have been documented after the largest outbreak in China in 2005, which was related to the consumption of raw pork or dishes containing pig’s blood. The major clinical features are sepsis or meningitis, with hearing loss a major complication of S. suis disease. Thai human S. suis isolates have shown diversity in serotypes and sequence types (STs), with serotype 2 and STs 1 and 104 being major genotypes. β-Lactam antibiotics can be used in empirical treatment for human S. suis infections; however, intermediate resistance to penicillin has been reported. Reducing S. suis incidence in Thailand requires a multidimensional approach, with combined efforts from the government and public health sectors through policy, regulations, education, and active surveillance.