Many people living with HIV/AIDS (PHA) use herbal medicine as one of alternative therapies, where curative options are limited. This study aimed to examine the association between the herbal medicine use and quality of life (QOL) among PHA in northeastern Thailand. Participants were 132 HIV-positive Thai adults who attended the PHA's self-help group meetings from June to July 2002. Health-related QOL scores were measured by self-administered questionnaire from the Medical Outcomes Study-HIV Health Survey. Dimensions of physical function (PF) and mental health (MH) in QOL were assessed. Additional data were collected on herbal medicine use, socio-demographic, psychosocial and HIV-related characteristics. The herbal medicine users had significantly better MH scores than the non-users, while the herbal medicine use was not statistically associated with PF scores. When stratified, herbal medicine users with the following characteristics had significantly better MH scores than the non-users: female, widowed, having no income, reporting any HIV-related symptom, having no instrumental support or receiving subsidies. In conclusion, herbal medicine use was associated with better MH especially among socially vulnerable PHA. This study suggests that herbal medicine has a potential to improve the MH aspect of QOL among socially vulnerable PHA who cannot easily receive antiretroviral therapy in Thailand.