Dimethyl sulfide (DMS), a volatile sulfur compound (VSC) found in mouth air, is thought to be associated with systemic diseases; this in contrast to the two other VSCs found in mouth air: hydrogen sulfide and methyl mercaptan (MM). This study aimed to validate the relationship between DMS in mouth air and oral and systemic factors. The subjects were 393 elderly Japanese volunteers participating in an oral and systemic health survey. They were surveyed for the concentration of VSC components in their mouth air and for their oral and systemic health status. Using logistic regression models, the prevalence of DMS in mouth air above the organoleptic threshold level (OTL) was found to be significantly associated with high-density lipoprotein (HDL) cholesterol level, medical history of colon polyps and asthma, being female, and the presence of MM in mouth air above the OTL. Our data suggest that systemic factors, such as a high serum HDL cholesterol level and a medical history of asthma and colon polyps, might be more prominent in subjects with elevated DMS. The differences, although statistically significant, are quite small. They also indicate that an oral factor, such as a high MM mouth-air level also influences the DMS mouth-air level in addition to systemic factors.