In a prospective two-group pilot study of a convenient sample of 156 young adults, we assessed improvement in HIV cognitive and transmission knowledge, hepatitis knowledge, and mental health at six-month follow-up. Multiple linear regression analysis revealed higher six-month scores in total HIV/AIDS knowledge, HIV/AIDS cognitive knowledge, HIV transmission knowledge and HBV and HCV knowledge at 6 months in the Hepatitis Health Promotion (HHP) group compared to the Art Messaging (AM) group. Moreover, homeless young participants who reported having significant others in their lives, and excellent or very good health did better than their counterparts. Youth who were attempting to get their lives together had higher scores for all types of knowledge except HBV. Hallucinogen users had significantly worse scores on all knowledge measures than non-users. Lastly, the HHP group revealed an improvement in psychological well-being compared to the AM group.