To date, existing studies have indicated that stigma against people living with HIV/AIDS (PLWHA) negatively affects their psychosocial well-being, and the impact may differ by age. In the current study, we aim to assess the impact of various types of stigma on PLWHA's psychological status and concomitant substance use. We explored different types of HIV stigma with psychosocial well-being and substance use employing mixed effect models among 2,987 Chinese PLWHA. Multivariate analyses revealed that each type of HIV stigma is positively associated with psychosocial distress, but negatively related to resilience and self-esteem across all age groups of PLWHA, with enacted stigma showing the strongest impact. Stigmatized PLWHA are more likely to smoke and use drugs, especially among the < 35 and 35-49-year-old groups. Age-specific interventions should be implemented to enhance PLWHA's stigma coping skill for improving their psychological health and reducing substance use in China and worldwide.