Indonesia’s total number of HIV/AIDS cases is still high. Inadequate knowledge about the risk of HIV infection will influence HIV prevention and therapy. This study aimed to map the level of HIV-related knowledge among Indonesians living on six major islands in Indonesia and investigate the relationship between socio-demographic characteristics and HIV/AIDS knowledge. This cross-sectional study used the Bahasa Indonesia version of the HIV Knowledge Questionnaire-18 items (HIV-KQ-18) Instrument. Data collection was done online through the Google form application. A total of 5,364 participants were recruited. The participants from Java had the highest degree of HIV/AIDS knowledge, which was 12.5% higher than participants from Sumatra, Kalimantan, Sulawesi, Papua, and Maluku. Linear regression showed that region, educational level, monthly expenditure, occupation, background in health sciences, and workshop attendance were significantly correlated with HIV knowledge. Participants typically understand that "HIV/AIDS transmission" only happens when sex partners are changed. Additionally, the government still needs improvement in HIV/AIDS education, particularly in the HIV incubation period, HIV transmission from pregnant women to the fetus, and condom use as one method of protection. There are disparities in HIV/AIDS knowledge levels among the major islands of Indonesia. Based on these findings, the government’s health promotion program to increase public awareness of HIV/AIDS must be implemented vigorously. Additionally, in line with our research findings, it is essential to broaden the scope of HIV/AIDS education and promotion materials.