Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) remain major public health problems among adolescents, who are vulnerable due to limited knowledge, inappropriate attitudes, and exposure to risky behaviors. Social media, particularly Instagram, has potential as a health education medium because it is accessible, visually engaging, and closely integrated into adolescents’ daily lives. This study aimed to analyze the effect of Instagram-based educational exposure on adolescents’ knowledge and attitudes toward HIV/AIDS at SMA X Padang in 2025. A quasi-experimental study with a pretest–posttest control group design was conducted. A total of 58 students were selected using simple random sampling and divided into an intervention group and a control group. The intervention group received HIV/AIDS educational content through the Instagram account “stop_hiv_aids” for one week, while the control group received no intervention. Data were collected using questionnaires before and after the intervention then analyzed using paired t-test and independent t-test, as well as Wilcoxon signed-rank test and Mann–Whitney U test. The results showed a significant difference in posttest scores between the control and intervention groups after the intervention for knowledge (p = 0.022) and attitudes (p = 0.000). Within-group analysis of the intervention group also demonstrated significant differences between pretest and posttest scores for knowledge (p = 0.000) and attitudes (p = 0.000). In conclusion, Instagram-based health education has a significant effect on improving adolescents’ knowledge and attitudes toward HIV/AIDS and can be utilized as an effective health promotion strategy for adolescents.